review article solid phase microextraction and related...

Review ArticleSolid Phase Microextraction and Related Techniques for Drugsin Biological Samples

Mohammad Mahdi Moein12 Rana Said2 Fatma Bassyouni3 and Mohamed Abdel-Rehim23

1 Department of Chemistry Amirkabir University of Technology Tehran Iran2Department of Analytical Chemistry Stockholm University SE10691 Stockholm Sweden3National Research Center of Egypt Cairo 12622 Egypt

Correspondence should be addressed to Mohamed Abdel-Rehim mohamedabdel-rehimanchemsuse

Received 27 August 2013 Revised 24 October 2013 Accepted 25 October 2013 Published 13 February 2014

Academic Editor Hiroyuki Kataoka

Copyright copy 2014 Mohammad Mahdi Moein et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

In drug discovery and development the quantification of drugs in biological samples is an important task for the determination ofthe physiological performance of the investigated drugs After sampling the next step in the analytical process is sample preparationBecause of the low concentration levels of drug in plasma and the variety of themetabolites the selected extraction technique shouldbe virtually exhaustive Recent developments of sample handling techniques are directed from one side toward automatizationand online coupling of sample preparation units The primary objective of this review is to present the recent developments inmicroextraction sample preparation methods for analysis of drugs in biological fluids Microextraction techniques allow for lessconsumption of solvent reagents and packingmaterials and small sample volumes can be used In this review the use of solid phasemicroextraction (SPME) microextraction in packed sorbent (MEPS) and stir-bar sorbtive extraction (SBSE) in drug analysis willbe discussed In addition the use of new sorbents such as monoliths and molecularly imprinted polymers will be presented

1 Introduction

Nowadays the analytical instrumentations can provide ahigh resolution separation and low detection limits down topicograms or below the whole progressive analytical processcan be wasted if an unsuitable sample preparation methodhas been employed Thus sample preparation is of crucialimportance for the analysis of drugs in biological samplesThe role of sample preparation is to remove interferencesand analyte preconcentration converting the analytes tosuitable form for separation and detection If an unsuit-able sample preparation method has been employed beforethe injection the whole analytical process may be wastedBecause of the low concentration levels of drug in plasmaand the variety of the metabolites the selected extractiontechnique should be virtually exhaustive In recent yearssolid phase microextraction (SPME) has been used by manyresearchers ever since it emerged in the early 1990s [1] SPMEtechnique has been widely used in many different areas such

as environmental analysis [2] food analysis [3] bioanalysis[4] drug monitoring [5] and toxicology [6] SPME can beused as direct immersion of the fiber into the sample toextract the analytes or introduction of the fiber in the sampleheadspace to extract volatile compounds that are partitionedbetween gaseous and liquid phases Many factors such aspH temperature salt concentration and stirring affect theequilibrium constant and equilibration time [7ndash16]

Another microextraction related technique is stir-barsorptive extraction (SBSE) which is an extraction techniquefor enrichment of volatile and semivolatile organic com-pounds having high extraction efficiency compared to SPMEbut has longer extraction time The technique has beenapplied effectively in environmental analysis mainly with gaschromatography-mass spectrometry (GC-MS) In additionthe SBSE technique was applied to some drugs in biologicalsamples in combination with GC-MS [17]

Recent development in solid phase microextractionrelated techniques is microextraction by packed sorbent

Hindawi Publishing CorporationJournal of Analytical Methods in ChemistryVolume 2014 Article ID 921350 24 pageshttpdxdoiorg1011552014921350

2 Journal of Analytical Methods in Chemistry

(MEPS) MEPS is the miniaturization of conventional SPEand can be connected online to GC or LC without anymodifications [18ndash22] The extraction steps in MEPS are thesame as in standard SPEmdashextraction loading washing andelutionmdashand these have to be optimized to obtain the highestanalyte recovery In MEPS solvent and sample volumes aresignificantly reduced compared to SPETheMEPS techniquehas beenused to extract awide range of drugs andmetabolitesin biological fluids such as urine plasma and blood [22]

This review presents recent developments of sample prep-aration in drug bioanalysis of complex fluids using SPMESBSE and MEPS

2 Solid Phase Microextraction (SPME) forDrug Analysis

In SPME the extraction is based on the partitioning of theanalyte between the organic phase on the fused silica fibreand the matrix Many factors such as pH temperature saltconcentration and stirring affect the equilibrium constantand the equilibration time [1] Fibre lifetime is a significantissue SPME fibre is quite sensitive to complex matrix such asplasma In addition type of polymer temperature durationand additives coming from the sample solution influence thestability of the coating It should be noted that additives suchas sodium hydroxide and salt could catalyse polymer thermaldegradation In some bioanalytical studies fibre life-time wasdecreased to about 20 samplings instead of 80 [8 9] In thetwo past decades SPME as a sample preparation method fordrug analysis has been used with various analysis methodsSPME was used with different separation techniques suchas capillary gas chromatography (CGC) [23ndash30] GCGC-MS [31ndash37] LCLC-MS [38ndash50] GC-ICP-MS [51ndash57] andHPLC-UVHPLC-MS [58ndash68]

21 Fiber and Monolithic In-Tube SPME In tube solid phasemicroextraction (in-tube SPME) is a new format of SPMEthat can be coupled online to LC for automated analysisof less volatile and polar compounds like drug metabolitesThis technique was used for the determination of drugs andmetabolites in different biological matrices like urine plasmaand cell culture media from in vitro assays [69ndash71] In addi-tion fiber in-tube SPME online with capillary electrophoresis(CE) was used for the analysis of amitriptyline imipraminenortriptyline and desipramine in human urine samples [72]In this work two types of Zylon fiber were used One ishigh modulus (HM) with heat treatment and the other isregular (AS) without heat treatment after spinning the fibersIn addition DB-5 capillary of 10mm length was packed witha fiber with the same length In order to investigate theeffect of the fiber and the capillary coating on extractionefficiency various kinds of extraction media were preparedas follows HM fiber packed in a DB-5 capillary HMDB-5 AS fiber packed in a DB-5 capillary ASDB-5 HM fiberpacked in an uncoated fused-silica capillary HMFS andonly DB-5 capillary DB-5 For the evaluation of the effectof the packing density on the extraction efficiency 26 and52 packed capillaries were prepared The packing density

has been calculated by using the average diameter of the fibersas 115 120583m The former was packed with 123 filaments andthe latter with 246 filaments in a 10mm DB-5 capillary [72]This method was then applied to the analysis of amitriptylinein human urine and the results showed that the hyphenatedsystem would be a powerful tool for the analysis of analytesin biological matrices DB-5 capillary was cut to 10mmlength and the fiber of the same length was packed intothis capillary In order to investigate the effect of the fiberand the capillary coating on extraction efficiency variouskinds of extractionmedia were prepared as follows HM fiberpacked in a DB-5 capillary HMDB-5 AS fiber packed in aDB-5 capillary ASDB-5 HM fiber packed in an uncoatedfused-silica capillary HMFS and only DB-5 capillary DB-5 For the evaluation of the effect of the packing density onthe extraction efficiency 26 and 52 packed capillaries wereprepared The packing density has been calculated by usingthe average diameter of the fibers as 115 120583mThe former waspacked with 123 filaments and the latter with 246 filaments ina 10mm DB-5 capillary The density is based on the volumeratio between the space and the filled part of the innercapillary in which the fibers were packedThe running bufferwas composed of 20mMNa2HPO4 buffer (pH 93) 06mM-cyclodextrin and 20 acetonitrile

Monolith in-tube SPME is another approach for druganalysis in complex matrix Different strategies were devel-oped for preparation of monolithic in tube SPME (Figure 1)A hybrid organic-inorganic silica monolith with ceyanoethylfunctional groups was synthesized by hydrolysis and poly-condensation of precursors via a two-step catalytic sol-gelprocess that was used as a sorbent for in-tube SPME [73 74]Briefly fused-silica capillaries (ID 250 120583m) were activatedwith 1M NaOH and then 1M HCl After rinsing with doubledistilled water they were dried at 160∘C under N

2flow

for 5 h The hybrid monolith was synthesized by hydrolysisand polycondensation of precursors via a two-step catalyticsol-gel process The optimal preparation conditions were asfollows 180 120583L of methanol 25120583L of 2M acetic acid 110 120583Loff CN-TEOS and 110 120583L of TEOS were mixed in a 15mLEppendorf vial After thorough vortexing the mixture wasleft for hydrolysis at 60∘C for 5 h After cooling to roomtemperature 10mg of N-dodecylamine was added to thesolution Then the pretreated capillary was filled to a certainlength with the sol by a syringe The capillary was sealedat both ends with silicone rubber and then was allowed tofurther react at 40∘C for 15 h Subsequently the capillarywas rinsed with ethanol to remove the N-dodecylamine andsoluble hydrolysis products and then dried at 60∘C for 48 hThe total and effective lengths of the hybrid silica monolithwere 20 and 15 cm respectively [74]

As it is shown in Figure 1 four capillaries are connected inthemodified cross connector to build the online fiber-in-tubeSPME-CE system To minimize the band broadening effectsthe gap between the separation capillaries must be strictlydecreased Therefore the capillaries between the two bufferreservoirs were connected using a microscope until the gapbetween the capillaries was less than 10 120583m In addition theSEM picture (Figure 1) showed that the monolith is attached

Journal of Analytical Methods in Chemistry 3

Sample

Autosampler

Waste

Waste

Valve A

Pump A

Pump B

LC column

Monolithiccapillary ESI

MS

Carriersolution

Mobilephase

Load position

Workstation

Inject position

loop

Valve Bemitter

(a)

(b) (c)

Figure 1 Construction of automated in-tube SPME-HPLCMS system and Scanning electron microscope images of the cross section of thehybrid silica monolith wide view (b) and close-up view (c) [74]

tightly to the inner-wall of the capillary The flow-throughpores size distribution determined by mercury porosimeterwas around 4m with a narrow size distribution whichresults in high permeability and favourable mass transfer inextraction applications

In another work a restricted access material (RAM)was employed for preparation of a lab-made biocompatiblein-tube SPME capillary that enables the direct injectionof biological fluids as well as the simultaneous exclusionof macromolecules by chemical diffusion barrier and drugpreconcentration [75 76] In this work silica particles (C18ndash45 120583m) were slurried in methanol and packed into 50mm

(length) of polyether ether ketone (PEEK) tubing (ID 002inch) and then the capillary column was capped at both endsby a 116 in (1 in = 254 cm) zero-volume union fitted with a10 120583m frit After this procedure the capillary was conditionedwith phosphate buffer (005mol Lminus1 pH 60) at a flow-rateof 10mLminminus1 for 20min Initially 50mL phosphate buffersolution (005mol Lminus1 pH 60) was percolated through thecapillary at a flow rate of 10mLminminus1 followed by 25mLBovine serum albumin solution 10mgmLminus1 (prepared inphosphate buffer solution) and by 25mL glutaraldehydesolution (25 vv) After 5 h the columns were washedwith 10mL sodium borohydride solution (10mgmLminus1) and


Analytical column

Fluorescence

RAM-BSA

Mobile phase

Mobile phase

Position A

To waste

Injection

Position B

detector

Fluorescence detector

Figure 2 Scheme of the operation mode of the six-port switchingvalve in the RAM in-tube SPME developed method [76]

then with 60mL water The RAM-BSA column was stored inphosphate buffer solution (005mol Lminus1 pH 74) at 4∘C Theschematic structure of RAM is shown in Figure 2

In addition monolithic molecular imprinted polymer(MIP) fiber based solid phase microextraction (SPME) wasdeveloped for selective and sensitive determination of dif-ferent drugs and biomarkers in biological samples [77 78]In situ polymerization of silica capillary mold using E astemplate was reported and in some studies the MIP fibers arepreparedand each fiber could be used for about 50 extraction-cycles without any significant decrease in extraction capacityFigure 3 illustrated the MIP strategy for preparation of MIPin tube SPME fiber

Other types of monolithic in tube SPME were preparedby different kinds of monomer and cross-linker mixturessuch as poly(acrylamide-ethylene glycol dimethacrylate)Poly(AA-EGDMA) monolith was selected as sorbent forSPME of three protoberberine alkaloids (Figure 4) BrieflyAA was weighed and put in a 1mL screw capped glassvial followed by adding isooctane toluene and methanol asporogen After AAwas completely dissolved the cross-linkerEGDMA and the initiator AIBN were added to the abovesolution Ultrasonication was applied for 20min to removedissolved oxygen Finally the prepolymerization solutionwasintroduced into the modified PEEK tube carefully and thenthe PEEK tube was sealed and put into a water bath for poly-merization (60∘C 3 h) After polymerization the monolith

was washed with acetonitrile to remove porogen and unre-acted reagents [79] poly(meta acrylic acid-ethylene glycol)[80ndash82] and poly(4-vinylpyridine-co-ethylene dimethacry-late) [83] Also in-tube SPMELC method was developedand validated for rifampicin interferon 120572

2a determinationin plasma samples for therapeutic drug monitoring and inplasma samples and lidocaine and its Metabolite MEGX inplasma samples [84ndash86]

In summary monolithic in-tube SPME was shown to bean appropriate method for drug metabolism studies and rou-tine analysis or pharmacokinetics as the parent compoundandmainmetabolites could bemonitored in variousmatricesof interest

22 Headspace Solid-Phase Microextraction (HS-SPME) inDrug Bioanalysis HS-SPME an alternative sample extrac-tion technique allows concentrating volatile and semivolatileanalytes from the headspace above the sample on a coatedfiber and to transfer the analytes from the fiber directly intothe injector port of a GC without further manipulations[87] Table 1 shows the different drugs and pharmaceuticalcomponents determined by HS-PME method

A schematic structure of HS-PME is shown in Figure 5[88] In someworks commercial fibers were used In additionthe sol-gel method was used for fiber preparation inHS-PMEtechnique In the following part we will describe differentkinds of precursors that were used in HSPME method

23 Sol-Gel HS-SPME The sol-gel process provides a usefulmethod of preparing organic-inorganic hybrid materialsthrough the hydrolysis and condensation of suitable metalalkoxides particularly silicone alkoxide which readily allowsforming three-dimensional (3D) network under relativelymild conditions [89]

Table 2 lists the names and chemical structures of theprincipal ingredients of the coating solution usedThe sol-gelprocess may involve mainly several parts as follows (1) ring-opening polymerization betweenKH-560 andDM-120573-CD (2)hydrolysis and polycondensation among the product of (1)TEOS and OH-TSO to generate a 3D network (3) chemicalanchoring of the polymeric networks to the outer surface ofthe fused-silica fiber (4) deactivating residual silanol groupson the stationary phase with PMHS aimed to reduce harmfuladsorptive effects Thus a surface-bonded polymeric coatingDM-120573-CDOH-TSO is formed as schematically representedin Figure 6 [90]

24 Molecularly Imprinted Polymers Solid Phase Microextrac-tion (MIPs-SPME) Molecularly imprinted polymers (MIPs)have proven to be useful materials in analytical chem-istry MIPs are cross-linked synthetic polymers obtainedby copolymerizing a monomer with a cross-linker in thepresence of a template molecule After polymerization thetemplate is removed from the porous network by washingleaving cavities in the polymeric matrix that are complemen-tary in size shape and chemical functionality to the templateThus the imprinted polymer is able to rebind selectively


Template monomers + initiator

Rubber Polymerization

Cut

Breaking and peeling the silica wall

with a blade5cm

1cm

60∘C24h

30 cm capillary

1120583m

100120583m

(a)

(b)

(c)

20kV times15000

20kV times150

Figure 3 Schematic illustration of MIP preparation procedure [78]

the analyte (the template) under certain experimental con-ditions [91]

Accordingly the combination of molecular imprintingand SPME would ideally provide a powerful analytical toolwith the characteristics of both technologies simplicity flex-ibility and selectivityThere are two strategies in this field theeasiest way for combining both technologies was proposed bymullet [92] which consisted of packing a capillary with theMIP particles for in-tube SPME andwas used for the selectivedetermination of propranolol in serum samples The devel-oped method was successfully applied and the advantagesof in-tube SPME were obvious (high enrichment factorsprovided by multiple draweject cycles ease of automationand fast operation) However this methodology is not free ofsome important drawbacks such as the lack of compatibilitybetween the solvent needed to desorb analytes from the MIPand themobile phase used (typical drawback of onlineMISPEprotocols) and the necessity of extra instrumentation (pumpmultiport valves)Thus the preparation of silica fibers coatedwith a MIP to perform SPME would be the best option anddifferent works have been developed in this field [91] Figures7 and 8 show schematic setup of these two strategies

Most papers that have been developed in MIP-SPMEfield are about fiber preparation for separation of differentvaluable targets of complex media such as Clenbuterol andStructural Analogues [93] triazines [94] diacetylmorphineand analogous compounds [95] Prometryn [96] bisphenolA [97 98] anabolic steroids [99] 221015840-bipyridine [100]antibiotic drugs [101] and sulfamethazine [102]

241 Preparation of MIP-Coated Fibers (MIP-CF) SPMEconditions based on theMIP-coated fibers are valuablemeth-

ods that developed in recent years As simple approachfor preparation of bisphenol A (BPA) MIP-coated SPMEfibers a capillary was inserted into a larger bore capillary toform a sleeve as mold [97] The prepolymer solution whichcomprisedBPA acrylamide (AM) 3-(trimethoxysilyl) propylmethacrylate (TRIM) AIBN and ACN was introducedinto the interspace between the two capillaries followedby polymerization under UV photoirradiation (Figure 9)The larger bore capillary was etched away with hydrofluoricacid after the polymerization This approach showed thatthis very simple method could become a routine preparationprocedure for MIP-coated fibers The MIP coating on thesilica fibers was homogeneous and porous and showed goodmechanical and chemical stability According to the result asof this work it was demonstrated that the MIP-coated fibershad better adsorptiondesorption kinetics compared with themonolith MIP fiber Under the optimized SPME conditionsselective extraction of BPA from standard mixture aqueoussample was feasible with the MIP-coated fibers

3 Stir-Bar Sorptive Extraction (SBSE)

Since SBSE was developed in 1999 [17] it has alreadyshown significance among the sorptive extraction techniquesSBSE and SPME are microextraction techniques with lowor even no consumption of organic solvents The analytesare extracted from the matrix into the polymer coatingimmobilized on a glass tube with a magnetic core Rapidmolecular-recognition equilibrium between adsorption anddesorption can be established since sampling is performedsimultaneously with the stirring As a result competitivesorption from an additional stirrer (eg magnet essential forthe SPME technique) can also be avoided [103]


NH2

OHOH

OHOH

OH OH

OHOH

2H+ + 2e 2H+ + 2e

Rearrangement

RearrangementHN

HN HN

Oxidation Oxidation

HO HO

PolymerizationCross-linking

HN

n

(a)

NH2

NH2

NH2

OH

OH

OH

OH

OH

OH

OH

OH

OH

OO

O

OO

OO

O

O

OO

O

O

O O

O

O

OSi

Si

Si

Dopamine

Tris-HCl

EGDMA AA AIBN

Polymerization

(A) (B) (C)

(b)

Figure 4 Schematic of (a) the formation of polydopamine layer and (b) modification of PEEK tube and preparation of poly(AA-EGDMA)monolith and Scanning electron micrograph of (A) polydopamine layer on the inner wall of PEEK tube (B) poly(AA-EGDMA) monolithand (C) interface of inner wall of PEEK tube and polymer monolith [79]

The main differences between the two techniques are thedesign of the extraction system and the amount of the sorbentmaterialThe sorbentmaterials are similar although till todaythe availability of commercial SBSEmaterials is rather limited[104] Contrary to SPME quantitative recoveries are oftenachievable with SBSE due to the clearly higher sample capac-ity SBSE can also be employed for the extraction of relatively

polar compounds Quantitative extraction can be achievedfor solutes with log 119870ow values of ca 4 and reasonableefficiencies are obtained for soluteswith log119870ow values above3 [105] For highly polar compounds similar approaches asfor SPME can be applied (ie derivatisation) Same as SPMEin SBSE various parameters such as type and thickness ofthe coating extraction time sample properties (pH ionic


Plunger

Stopper

Adjustableneedleguidedepthgauge

Septumpiercingneedle

Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

Figure 5 SPME high-temperature headspace sampling [88]

strength) agitation temperature and analyte desorptioncould be evaluated The extraction time is typically longerthan in SPME because the amount of coating is greater andit takes longer to reach equilibrium The analyte desorptionis more critical for SBSE than for SPME likewise due tothe greater amount of coating A high flow rate of gas (upto 100mLminminus1) is recommended for fast desorption ofanalytes during thermal desorption [105]

31 Sol-Gel Technology in Stir-Bar Sorptive Extraction Forthe first time Liu et al [106] used sol-gel technology in stir-bars to produce a partially hydroxyterminated-PDMS coatedstir-bar which was used for extracting a group of PAHs andorganophosphorous compounds

The sol-gel process offers a convenient versatile pathwayfor preparing advanced inorganic and organic-inorganichybrid material systems with tunable porosity selectivityand thermal and chemical stability The schematic of sol-gelreactions is shown in Figure 10 (where methyltrimethoxysi-lane (MTMOS) and hydroxy-terminated polydimethylsilox-ane (PDMS) are shown to represent sol-gel precursor and sol-gel active organic polymer resp) [107]

Despite its numerous advantages over conventionalSPME fibers SBSE also suffers from serious limitations [107]as follows

(1) limited number of commercially-available coatings(2) coating is not chemically bonded to the substrate

leading to the possibility of bleeding at even rela-tively low temperature during thermal desorption and

transfer of the extracted analytes from the stir-bar tothe GC system

(3) coating is vulnerable to washing away if propersolvent is not used during solvent desorption

(4) thermal desorption requires an expensive thermaldesorption unit

(5) thick highly viscous polymeric sorbents used onthe stir-bar require hours to reach the extractionequilibrium

(6) there is a need for a relatively high volume of backextraction solvent which evidently dilutes the pre-concentrated analytes

High porous sol-gel PDMS coated stir-bar with 30 120583mcoating thickness was developed by Liu et al [106] Thecoating was found thermally stable up to 300∘C The sol-gelPDMS coated stir-bars were tested for the extraction of 119899-alkanes PAHs and organ phosphorus pesticides The sol-gelPDMS coated stir-bar reached extraction equilibrium in lessthan 15min In addition unlike commercial PDMS coatedstir-bars the sol-gel PDMS coated stir-bar is equally suitablefor both polar and nonpolar analytes

Different sorbents for SBSE sol-gel method were devel-oped in recent years A sol-gel PDMSPVA coated stir-barfor the extraction of organophosphorus pesticides (OPPs) inhoney samples was used [108] The extracted analytes wereback-extracted by solvent desorption The back-extractionsolvent which contained the analyte(s) of interest wasthen injected into the GC using large volume injectionfollowed by GC-FPD The extraction performance of sol-gel CWPDMSPVA was compared with commercial PDMSstir-bar and CarboxenPDMS SPME fiber using headspaceextraction Sol-gel CWPDMSPVA coated stir-bar demon-strated the highest sorption capacity and sim10 times highersensitivity [109] Also a sol-gel PDMS120573-CD coating (30ndash150 120583m) for the extraction of polar compounds from dif-ferent matrices (eg estrogens in environmental water andbisphenol A in drinking water) [110] The same sol-gelsorbent (sol-gel PDMS120573-CD) was utilized for extractingbrominated flame retardants from soil and dust samplesemploying ultrasound-assisted extraction followed by HPLCanalysis [111] SBSE performances were compared for fourdifferent sol-gel coatings including PDMSb-CD PDMSCWPDMSPVA and PDMSPVA The sol-gel PDMS120573-CDcoated stir-barwas found to be themost efficient for the targetcompounds In addition to superior extraction performancesol-gel PDMS120573-CD coated stir-bars demonstrated excellentdurability and no discernible loss of extraction efficiency wasobserved even after 100 extraction cycles

32 Molecularly-Imprinted Stir-Bar Sorptive Extraction (MI-SBSE) MI-SBSE is based on the partitioning of target ana-lytes between a liquid sample and a stationary phase-coatedstir-bar Until now only polydimethylsiloxane (PDMS)coated stir-bars are commercially available restricting therange of applications to the extraction of hydrophobic com-pounds (organochlorine and organophosphorus pesticides)


Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys

Polydimethylsiloxane

Hum

anbloo

dGCMS

[160]

Illegaldrugs(acetylated

amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop

oxypheneimipramineacetylated

codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als

Polydimethylsiloxane-

divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia

Polydimethylsiloxanedivinylbenzene

(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m

polydimethylsiloxanedivinylbenzene

(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron

esAntiepilepticdrugs


(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo

lydimethylsiloxanedivinylbenzene

(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro

mSupelco(BellefontePA

USA

)

Rabbitplasmaessential

oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m

polyacrylate65120583

mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen

(CAR)PDMSand5030120583

mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic

Nanostructureda-carboxy

Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero

fheavyprenatalalcoho

lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]


Table 2 Function and chemical structures of the coating solution ingredients for sol-gel-derived DM-120573-CDOH-TSO coating [34]

Name Function Chemical structure

TEOS Sol-gel precursor H5C2O

OC2H5

OC2H5

OC2H5Si

KH-560 Coupling reagent Si

OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi

DM-120573-CD Coating

OCH3

OCH3

O

O

OH

7

PMHS Deactivation reagent SiSiSiSi

CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r

TFA (95) Acid catalyst CF3COOH

due to the polar character of PDMS Besides the MIP-coated stir-bars showed not only the expected high selectivitybut also rapid equilibrium adsorption thanks to the porousnature of the imprinted polymer obtained combined with asuitable thickness of coated polymer film (120583160ndash180 lm) [112]More recently the use of MIP-coated stir-bars prepared bychemical bonding of theMIP to the stir-bar through silylationof the substrate surface and then multiple copolymerizationreaction was proposed for the determination of variouscomponents in different samples [113ndash117] The schematicdiagrams of the preparation of MIP-SBSE coating usingterbuthylazine as template molecule is shown in Figure 11[114]

33 Stir-Bars Sorptive Extraction Based on Monolithic Mate-rial (SBSEM) and Molecularly Imprinted Polymer MonolithMicroextraction (MIPMME) The preparation of monolithicmaterials is very simple just by polymerization of a monomermixture with a porogen solvent forming a porous poly-mer In this way Huang and Yuan developed monolithicmaterial obtained by in situ copolymerization of octylmethacrylate and ethylene dimethacrylate in the presenceof a porogen solvent containing 1-propanol 14-butanediol

and water with azobisisobutyronitrile as the initiator [118]The results demonstrate that prepared stir-bar was suitablefor preconcentration of both apolar and polar analytes Theenrichment factors for phenanthrene anthracene and pyrenewere 150 134 and 189 respectively The SBSEM shows goodbatch-to-batch reproducibility and good stability and canbe reused at least 10 times for the extraction of polycyclicaromatic hydrocarbons in seawater (Figure 12)

In another in situ copolymerization approach vinylpyr-rolidone and divinylbenzene in the presence of a porogensolvent containing cyclohexanol and 1-dodecanol with azo-bisisobutyronitrile as initiator were used for SBSEM prepa-ration [119] Polycyclic aromatic hydrocarbons were used toinvestigate the extraction efficiencies of SBSEM for apolaranalytes Hormones aromatic amines and phenols wereselected as test analytes to investigate the extraction efficien-cies of SBSEM for weakly and strongly polar compoundsTheresults showed that the new SBSEM could enrich the above-mentioned organic compounds effectively It is worthy tomention that the SBSEM can enrich some heavy metal ionssuch as Cu2+ Pb2+ Cr3+ and Cd2+ through coordinationadsorption

In another case poly(vinylpyridine-ethylene dimethacry-late) is used as SBSEM combined with high performance


CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn

Figure 6 The chemical structure of the DM-120573-CDOH-TSO coating [34]

30 cm

Removal of protecting polymer layer1 cm 5 cm

Filling with polymerisation mixture

Polymerisation at 65∘C

3M NH4HF2

Removal of silica

Figure 7 Preparation of molecularly imprinted fiber [91]

liquid chromatography with diode array detection underthe optimized experimental conditions for analysis of targetcompounds inwastewater samples [120]Themethod showedgood linearity and repeatability as well as advantages such assensitivity simplicity low cost and high feasibility

4 Microextraction by Packed Sorbent (MEPS)

MEPS was recently introduced as a novel method for samplepreparation being a miniaturization of the conventionalSPE technique in which the sample volume extraction and


From pump

In-tube MIP SPME capillary(extraction)

Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column

MIP particles (imprinted with analyte)

Analyte

Interferents

UV detector

Data acquisitionand analysis

Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column

In-tube MIP SPME capillary(desorption)

UV detector


Six-port valve

(b)

Figure 8 Schematic representation of in-tube MIP SPME configuration (a) Load position (extraction) (b) injection position (desorption)[92]

washing solvents volumes are greatly reduced compared toSPE MEPS differs from commercial SPE in that the packingis integrated directly into the syringe and not into a separatecolumn Moreover the packed syringe can be used severaltimes more than 100 times using plasma or urine sampleswhereas a conventional SPE column is used only once MEPScan handle small sample volumes (10120583L plasma urine orwater) as well as large volumes (1000120583L)

The extraction steps in MEPS are the same as in standardSPE extraction washing and elution and these have to beoptimized to obtain the highest analyte recovery In MEPS

extraction procedures additional steps for postcleaning andreconditioning have to be included to enable multiple usesof the MEPS sorbent Blood samples require dilution of20ndash25 times with water or acidic water while 4-5 timesdilution is needed for plasma samples Using mixed-mode(anion-cation exchange) the sample pH has to be adjusted toproduce charged analytes MEPS was used with real samplesfrom clinical institutions or pharmaceutical industry forestablished drugs and new drug candidature (Figure 13)

The superior performance of MEPS was recently illus-trated by online LC-MS and GC-MS assays of drugs and


HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi

PolymerizationTRIM AIBN

Removing oradsorbing BPA

+

C2H

(a) (b)

Figure 9 The preparation process of BPA-imprinted MIP coating on the silylated wall of the silica capillaries Schematic representation ofBPA-imprinted MIP coating on the silylated wall of the silica capillaries and Scanning electron micrographs of MIP coating of the fiber (a)times200 (b) times20000 [97]

metabolites in water urine plasma and blood samples [18ndash22 121ndash153] The combination of MEPS and liquid chro-matography mass spectrometry (LC-MS) is a good tool forthe screening and determination of drugs and metabolitesin blood plasma and urine samples Mass spectrometry ispresently one of themost powerful detection techniques par-ticularly in pharmaceutical analysis where good selectivityand high sensitivity are often needed MEPS significantlyreduces the volume of solvent and sample needed Thisapproach to sample preparation is very promising for manyreasons (1) it is easy to use (2) it is a fully automated onlineprocedure (3) it is rapid and (4) the cost of analysis isminimal compared to conventional solid-phase extraction

41 MEPS Extraction Procedures Plasma samples werediluted four times while blood samples diluted 20 times withwater(i) Conditioning Step The sorbent was conditioned with150 120583L methanol and subsequently with 150120583L water

(ii) Sample Loading Step Sample can be loaded by multipleaspirates-dispenses cycles (5 times 100 120583L)

(iii) Washing Step The sorbent was washed after sampleloading by 150120583L water

(iv) Elution of the Analytes Elution solution was organicsolvent (ge60)

The MEPS technique has been used to extract a widerange of analytes in different matrices (urine plasma andblood) Hence several drugs such as local anesthetics andtheir metabolites the anticancer drugs roscovitine olo-moucine busulphan cyclophosphamide and AZD3409 the120573-blockers acebutolol and metoprolol the neurotransmit-ters dopamine and serotonin methadone and cocaine andcocaine metabolites have been extracted from biologicalsamples such as blood plasma or urine samples using MEPS[18ndash22 121ndash153] Table 3 shows the application of MEPStechnique in different matrices and various types of drug


CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis

Acidbasefluoride catalyst

Hydrolyzed sol-gel precursor


HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation

Growing sol-gel network

Growing sol-gel network Sol-gel network with integrated PDMS

Sol-gel network with integrated PDMS Surface-bonded sol-gel PDMS coating

Hydroxy-terminated PDMS

Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si

Si Si Si Si Si Si SiSiSi

Si Si Si Si Si Si Si Si Si Si

Sim

m

m

m

n

n

n

n

n

n HO

Figure 10 Chemical reactions involved in the synthesis of surface-bonded sol-gel hybrid organic-inorganic polymeric network [107]

42 Molecularly Imprinted Polymer as Sorbent in MEPSMolecularly imprinted polymer was used as extracting sor-bent in MEPS for the simultaneous determination of fourlocal anaesthetics (ropivacaine lidovacaine bupivacaine andmepivacaine) in human plasma and urine samples have beenevaluated In comparison with protein precipitation MIP-MEPS offer enrichment of analytes and elimination of inter-ferences from matrix constituents This may be importantfor increasing sensitivity and for robustness of the LC-MSsystem Ion suppressionwas observed in protein precipitationmethod for lidocaine ropivacaine and mepivacaine Thematrix effect was more pronounced using protein precipi-tation The matrix effect (ME) for these substances rangedfrom 50 to 146 using protein precipitation while it wasless than 20 using MIP-MEPS This suggests that cleanerextracted samples can be obtained with MEPS and thatmatrix related problems can be reduced [147] In comparisonwith conventional SPE theMEPSmethod can handle smallersample volumes (10ndash100 120583L) This is mainly an advantage forsamples from children

43 Extraction of Proteins from Plasma by MEPS MEPStechnique online with LC-MSMS was used for the quan-tification of SNSR receptors agonist peptide BAM8-22 andantagonist BAM22-8 in plasma samples [148] MEPS-C8 was

used and spiked plasma sample (125 120583L) was diluted (1 1)with 01 CHOOH in water 50 120583L were drawn onto theMEPS-syringe three times The sorbent was then washedonce with 50120583L of 5 methanol in water to remove otherinterferences The analytes were then eluted by 40 120583L 025ammonium hydroxide in methanol-water 95 5 (vv) directlyinto LC injector The calibration curve in plasma was inthe range of 200ndash3045 nmolL The regression correlationcoefficients for plasma samples were ge099 The between-batch accuracy and precision for BAM8-22 ranged fromminus13 to minus20 and 40 to 14 respectively Additionally theaccuracy and precision for BAM22-8 ranged from minus13 to 70and from 30 to 12 respectively The method was used forpharmacokinetic studies for BAMs in plasma samples [148]MEPS technique provided significant advantages such as thespeed and the simplicity of the sample-preparation processCompared with other extraction techniques such as proteinprecipitation and ultrafiltration MEPS gave cleaner samplesand higher recovery (gt90)Themethod had good accuracyand good precision within the studied calibration rangeFurthermore the method reduced the sample preparationtime for BAMs (less than oneminute per sample) which is ofgreat importance to handle unstable analytes such as BAMs inplasma andblood samplesThemethodwas applied to plasmasamples from preclinical studies [148] The potential savingsin handling time reduced solvent useThe simplicity ofMEPS


Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+

Silanization of glass capillary

Si O

OO

O

O

Si O

OO

O

O

Polymerization

Cross linkerInitiator

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl

Terbuthylazine(template)

N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly

Desorbingterbuthylazine

Extractingterbuthylazine

Coating of terbuthylazine MIP-coated stir bar

O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)

Figure 11 Schematic diagrams of the preparation of MIP-SBSE coating using terbuthylazine as template molecule and Scanning electronmicrographs of the surface structure of the MIP- and NIP-coated stir-bar (a) and (c) are the NIP coating for magnitude of 100 and 5000respectively (b) and (d) are the MIP coating for magnitude of 100 and 5000 respectively [114]

technique will continue to attract interest among analyticalchemists searching for improved analysis methods

In summary the significant advantages of MEPS arereduction in the amount of sorbent bed solvents and samplepreparation times and reduction in carry-over effects

5 Monolithic Packed 96-Tips for HighThroughput Bioanalysis

Recently we introduced a 96-tips set packed with a plug of amonolithic adsorbent Using such a set it is possible to handle


Table 3 Extraction of different analytes by MEPS technique

Components Sample matrix MEPS sorbent ReferencesMethadone Human urine Silica-C8 [19]

Dopamineserotonin Human urine Silica-C8 [20]

Cocainemetabolites Human urine Silica-C8 [21]

Clozapinemetabolites Dried blood spots Silica-C8 [121]Methadonebuprenorphinenorbuprenorphinenaloxonelevosulpiride Plasma Silica-C8 [122]

Pravastatinpravastatin lactone Rat plasmaurine Silica-C8 [123]Immunosuppressive drugs (Cyclosporine everolimusSirolimus tacrolimus) Whole blood Silica-C8 [124]

Oxcarbazepinemetabolites Plasmasaliva Silica-C18 [125]

Antiepileptic drugs Human plasmaurine Silica-C18 [126]

Amiodaronedesethylamiodarone Human plasma Silica-C18 [127]

Methadone Dried blood spots Silica-C18 [128]

Biogenic amines Human urine Silica-C18 [129]

Metabolites of monoterpenes Human urine C18silica phases [130]

Acebutolol metoprolol Human plasmaurine Polystyrene polymer [131]

Busulphan Human plasma Polystyrene polymer [132]

Linezolid and amoxicillin Human plasma (C2 C8 C18 M1 (80 C8 and20 SCX) and Sil (pure silicate))

[133]

Cotinine Human urine (C2 C8 C18 silica and C8SCX) [134]

Psychotropic drugs Human serum C18 C8 and C8-SCX [135]

Antipsychotic drugs Human plasma 80 C8 and 20 SCX [136]

Local anaesthetics Human plasma Benzenesulphonic acid cationexchange silica

[137]

Ropivacaine metabolites Human urine Polystyrene polymer ISOLUTEENV+

[138]

Lidocaine glycylxylidide (GX) monothylglycylxylidide (MEGX)and 3-OH lidocaine Human plasmaurine

Silica based (C8) polymer based(ENV+) and a methacrylatebased organic monolith

[139]

Antidepressants Human plasma C8strong cationic exchange [140]

Ropivacaine Human plasma Methylcyanopropylsilarylene(5050)

[141]

Ropivacaine lidocaine bupivacaine mepivacaine Human plasma Molecularly imprinted polymers(mips)

[142 147]

Cyclophosphamide Human plasma C2-sorbent [143]

Codeine metabolites Human urineBarrel insert needle (BIN)

poly(styrene co-divinylbenzene)(PS DVB)

[144]

Propranolol metoprolol verapamil Human urine C2 C8 C18 M1 (cationexchanger) and Sil (pure silica)

[145]

Bam peptide Human plasma C8 [148]

a 96-well plate in only 2 minutes [154] Packed 96-tips sam-ple preparation is a clean highthroughput and automatedsample-preparation method Samples are prepared in a 96-well plate format and the analytes adsorb onto the polymer-based monoliths in the extraction step The next step purifiesthe sample by washing the sorbent with an appropriatewashing solution In a final step the analytes were directly

eluted into a 96-well plate using an appropriate solvent forthe analytes and the subsequent instrumental analysis

51 Preparation of Monolithic Plug in Tips The polymer-ization mixture of methacrylate monoliths consists of asolution containing glycidyl methacrylate (20) ethyleneglycol dimethacrylate (155) butyl methacrylate (35)


Table 4 Applications of monolithic methacrylate polymer packed 96-tip

Compound classcompound Sample matrix Sample volume (120583L) Analytical method Calibration range ReferencesLocal anaesthetics

Lidocaine Human plasma 100 LC-MSMS 14ndash5000 nM [154]Ropivacaine Human plasma 100 LC-MSMS 2ndash2000 nM [155]Bupivacaine Human plasma 100 LC-MSMS 2ndash2000 nM [156]

Anticancer drugsCyclophosphamide Mice blood 20 LC-MSMS 10ndash2000 nM [159]Busulphan Human blood 100 LC-MS 5ndash2000 nM [159]Roscovitine Human plasma 100 LC-MSMS 14ndash5000 nM [154]120573-Blockers

Pindolol Human plasma 100 LC-MSMS 05ndash5000 nM [157 158]Metoprolol Human plasma 100 LC-MSMS 05ndash5000 nM [157 158]

Figure 12 Photograph of different dimensions of SBSEM [118]

Packing material(1-2mg)

Figure 13 MEPS syringe with sorbent

Figure 14 Monolithic packed 96-tips

AIBN (1 wt with respect to monomers) and 1-dodecanol(30) and cyclohexanol (30) was vortexed for 10minand purged with nitrogen for 10min in order to removeoxygen The pipette tips were filled with about 8mm (6-7 120583L) by the capillary action and placed vertically insidethe polymerization apparatus The polymerization using UVlight at 254 nm was allowed to proceed first for 60min withthe sharp end of the tip down and at a distance to thelamp of 15 cm and then for 25min with the sharp end upand at a distance of 5 cm to the lamp After completionof polymerization the tips were removed inspected undermicroscope for bubbles and washed with acetone to removethe porogenic solvents and other compounds remaining inthe monolith (Figure 14)

The key aspect of the monolithic phase is that monolithicmaterial can offer both good binding capacity and low back-pressure properties compared to for example silica phasesUsing this device a 96-well plate could be handled in 2ndash4minutes

52 Monolithic Packed 96-Tips Application in BioanalysisEvaluation of monolithic packed 96-tips for the extractionof drugs [154ndash159] such as anticancer drugs (busulphancyclophosphamide roscovitine) 120573-blocker drugs (metopro-lol pindolol) and local anesthetics (lidocaine ropivacainebupivacaine) from human plasma or blood samples hasbeen developed and validated (Table 4) Utilizing plasmasamples the tips could be used several times (5 times)and still get good results Utilizing blood samples packedtips could only be used once The results showed that themethod is selective and accurate It was shown that smallsample volumes can be handled solvent consumption waslow and the procedure was very fast (2min per 96-well plate)(Table 4) Application of monolithic methacrylate polymerpacked 96-tips in bioanalysis

6 Conclusions

The advantages of various kinds of SPME SBSE and MEPSas powerful sample preparation methods in bioanalysis havebeen demonstrated and illustrated in many cases It is clear


that the number of the papers published in this research areahas increased during the last decade In addition the resultsshowed the ability of these techniques for determination ofdrugs in biological samples Future work should be focusedon finding of more selective high throughput adsorptioncapacity and stable sorbents with capability for extraction oflarge molecules

Conflict of Interests

We declare that there is no conflict of interests in this work

References

[1] C LArthur and J Pawliszyn ldquoSolid phasemicroextractionwiththermal desorption using fused silica optical fiberrdquo AnalyticalChemistry vol 62 pp 2145ndash2148 1990

[2] J LMartinezVidal P Plaza-Bolanos R Romero-Gonzalez andA Garrido Frenich ldquoDetermination of pesticide transforma-tion products a review of extraction and detection methodsrdquoJournal of Chromatography A vol 1216 no 40 pp 6767ndash67882009

[3] H H Jelen M Majcher and M Dziadas ldquoMicroextractiontechniques in the analysis of food flavor compounds a reviewrdquoAnalitica Chimica Acta vol 738 pp 13ndash26 2012

[4] G Ouyang D Vuckovic and J Pawliszyn ldquoNondestructivesampling of living systems using in vivo solid-phase microex-tractionrdquo Chemical Reviews vol 111 no 4 pp 2784ndash2814 2011

[5] HKataoka ldquoRecent developments and applications ofmicroex-traction techniques in drug analysisrdquo Analytical and Bioanalyt-ical Chemistry vol 396 no 1 pp 339ndash364 2010

[6] F Pragst ldquoApplication of solid-phase microextraction in ana-lytical toxicologyrdquo Analytical and Bioanalytical Chemistry vol388 no 7 pp 1393ndash1414 2007

[7] R Eisert and J Pawliszyn ldquoDesign of automated solid-phasemicroextraction for trace analysis of organic compounds inaqueous samplesrdquo Journal of Chromatography A vol 776 no2 pp 293ndash303 1997

[8] M Abdel-Rehim M Andersson E Portelius C Norsten-Hoog and L Blomberg ldquoDetermination of ropivacaine and itsmetabolites in humanplasmausing solid phasemicroextractionand GC-NPD GC-MSrdquo Journal of Microcolumn Separationsvol 13 no 8 pp 313ndash321 2001

[9] M Abdel-Rehim Z Hassan L Blomberg and M HassanldquoOn-line derivatization utilizing solid-phase microextraction(SPME) for determination of busulphan in plasma using gaschromatography-mass spectrometry (GC-MS)rdquo TherapeuticDrug Monitoring vol 25 no 3 pp 400ndash406 2003

[10] X Zhang A Es-haghi F M Musteata G Ouyang and JPawliszyn ldquoQuantitative in vivo microsampling for pharma-cokinetic studies based on an integrated solid-phase microex-traction systemrdquo Analytical Chemistry vol 79 no 12 pp 4507ndash4513 2007

[11] D Vuckovic E Cudjoe FMMusteata and J Pawliszyn ldquoAuto-mated solid-phase microextraction and thin-film microex-traction for high-throughput analysis of biological fluids andligand-receptor binding studiesrdquo Nature Protocols vol 5 no 1pp 140ndash161 2010

[12] S Risticevic Y Chen L Kudlejova et al ldquoProtocol for the devel-opment of automated high-throughput SPME-GCmethods for

the analysis of volatile and semivolatile constituents in winesamplesrdquo Nature Protocols vol 5 no 1 pp 162ndash176 2010

[13] J Lipinski ldquoAutomated solid phase dynamic extractionmdashextraction of organics using a wall coated syringe needlerdquoFreseniusrsquo Journal of Analytical Chemistry vol 369 no 1 pp 57ndash62 2001

[14] D W Lachenmeier L Kroener F Musshoff and B MadealdquoApplication of tandem mass spectrometry combined with gaschromatography and headspace solid-phase dynamic extrac-tion for the determination of drugs of abuse in hair samplesrdquoRapid Communications in Mass Spectrometry vol 17 no 5 pp472ndash478 2003

[15] H Bagheri Z Ayazi and H Sistani ldquoChemically bonded car-bon nanotubes onmodified gold substrate as novel unbreakablesolid phase microextraction fiberrdquo Microchimica Acta vol 174no 3 pp 295ndash301 2011

[16] D Lenz L Kroner and M A Rothschild ldquoDetermina-tion of gamma-hydroxybutyric acid in serum and urine byheadspace solid-phase dynamic extraction combined with gaschromatography-positive chemical ionization mass spectrome-tryrdquo Journal of Chromatography A vol 1216 no 18 pp 4090ndash4096 2009

[17] E Baltussen F David H Janssen P Sandra and C CramersldquoStir bar sorptive extraction (SBSE) a novel extraction tech-nique for aqueous samples theory and principlesrdquo Journal ofMicrocolumn Separations vol 11 no 10 pp 737ndash747 1999

[18] M Abdel-Rehim ldquoNew trend in sample preparation on-linemicroextraction in packed syringe for liquid and gas chro-matography applications I Determination of local anaestheticsin human plasma samples using gas chromatography-massspectrometryrdquo Journal of Chromatography B vol 801 no 2 pp317ndash321 2004

[19] A El-Beqqali and M Abdel-Rehim ldquoQuantitative analysisof methadone in human urine samples by microextractionin packed syringe-gas chromatography-mass spectrometry(MEPS-GC-MS)rdquo Journal of Separation Science vol 30 no 15pp 2501ndash2505 2007

[20] A El-Beqqali A Kussak and M Abdel-Rehim ldquoDetermi-nation of dopamine and serotonin in human urine samplesutilizing microextraction online with liquid chromatogra-phyelectrospray tandem mass spectrometryrdquo Journal of Sepa-ration Science vol 30 no 3 pp 421ndash424 2007

[21] E Jagerdeo and M Abdel-Rehim ldquoScreening of cocaine and itsmetabolites in human urine samples by direct analysis in real-time source coupled to time-of-flight mass spectrometry afteronline preconcentration utilizing microextraction by packedsorbentrdquo Journal of the American Society for Mass Spectrometryvol 20 no 5 pp 891ndash899 2009

[22] M Abdel-Rehim ldquoRecent advances in microextraction bypacked sorbent for bioanalysisrdquo Journal of Chromatography Avol 1217 no 16 pp 2569ndash2580 2010

[23] M Krogh K Johansen F T Cnnesen and K E RasmussenldquoSolid-phase microextraction for the determination of the freeconcentration of valproic acid in human plasma by capillary gaschromatographyrdquo Journal of Chromatography B vol 673 no 2pp 299ndash305 1995

[24] S Ulrich and J Martens ldquoSolid-phase microextraction withcapillary gas-liquid chromatography and nitrogen-phosphorusselective detection for the assay of antidepressant drugs inhuman plasmardquo Journal of Chromatography B vol 696 no 2pp 217ndash234 1997


[25] H G Ugland M Krogh and K E Rasmussen ldquoAqueousalkylchloroformate derivatisation and solid-phasemicroextrac-tion determination of amphetamines in urine by capillary gaschromatographyrdquo Journal of Chromatography B vol 701 no 1pp 29ndash38 1997

[26] M Krogh H Grefslie and K E Rasmussen ldquoSolvent-modifiedsolid-phase microextraction for the determination of diazepamin human plasma samples by capillary gas chromatographyrdquoJournal of Chromatography B vol 689 no 2 pp 357ndash364 1997

[27] MAbdel-RehimGCarlssonM Bielenstein TArvidsson andL G Blomberg ldquoEvaluation of solid-phase microextraction forthe study of protein binding in human plasma samplesrdquo Journalof Chromatographic Science vol 38 no 10 pp 458ndash464 2000

[28] M Vita M Abdel-Rehim C Nilsson et al ldquoStability pKa andplasma protein binding of roscovitinerdquo Journal of Chromatogra-phy B vol 821 no 1 pp 75ndash80 2005

[29] D D l C Garcıa M Reichenbacher K Danzer C HurlbeckC Bartzsch and K H Feller ldquoAnalysis of wine bouquet com-ponents using headspace solid-phasemicroextraction-capillarygas chromatographyrdquo Journal of Sepration Science vol 21 no 7pp 373ndash377 1998

[30] M H de Oliveira M E C Queiroz D Carvalho S MSilva and F M Lancas ldquoDetermination of diazepam inhuman plasma by solid-phasemicroextraction and capillary gaschromatography-mass spectrometryrdquo Chromatographia vol62 no 3-4 pp 215ndash219 2005

[31] N G Orellana-Velado R Pereiro and A Sanz-Medel ldquoSolidphase microextraction gas chromatography-glow discharge-optical emission detection for tin and lead speciationrdquo Journalof Analytical Atomic Spectrometry vol 16 no 4 pp 376ndash3812001

[32] K J Reubsaet H R Norli P Hemmersbach and K ERasmussen ldquoDetermination of benzodiazepines in humanurine and plasma with solvent modified solid phase microextraction and gas chromatography rationalisation of methoddevelopment using experimental design strategiesrdquo Journal ofPharmaceutical and Biomedical Analysis vol 18 no 4-5 pp667ndash680 1998

[33] F Luo Z Wu P Tao and Y Cong ldquoPreparation by low-temperature nonthermal plasma of graphite fiber and its char-acteristics for solid-phase microextractionrdquo Analytica ChimicaActa vol 631 no 1 pp 62ndash68 2009

[34] J Zhou and Z Zeng ldquoNovel fiber coated with 120573-cyclodextrinderivatives used for headspace solid-phase microextraction ofephedrine and methamphetamine in human urinerdquo AnalyticaChimica Acta vol 556 no 2 pp 400ndash406 2006

[35] M E C Queiroz S M Silva and D Carvalho ldquoDetermina-tion of lamotrigine simultaneously with carbamazepine carba-mazepine epoxide phenytoin phenobarbital and primidone inhuman plasma by SPME-GC-TSDrdquo Journal of ChromatographicScience vol 40 no 4 pp 219ndash223 2002

[36] C Deng W Zhang J Zhang and X Zhang ldquoRapid determi-nation of acetone in human plasma by gas chromatography-mass spectrometry and solid-phase microextraction with on-fiber derivatizationrdquo Journal of Chromatography B vol 805 no2 pp 235ndash240 2004

[37] L Hu and D Y Chen ldquoApplication of headspace solid phasemicroextraction for study of noncovalent interaction of borneolwith human serum albuminrdquo Acta Pharmacologica Sinica vol30 no 14 pp 1573ndash1576 2009

[38] A Aresta C D Calvano F Palmisano and C G ZamboninldquoDetermination of clenbuterol in human urine and serum by

solid-phase microextraction coupled to liquid chromatogra-phyrdquo Journal of Pharmaceutical and Biomedical Analysis vol 47no 3 pp 641ndash645 2008

[39] B J G Silva R H C Queiroz and M E C QueirozldquoSimultaneous determination of nontricyclic antidepressantsin human plasma by solid-phase microextraction and liquidchromatography (SPME-LC)rdquo Journal of Analytical Toxicologyvol 31 no 6 pp 313ndash320 2007

[40] M E C Queiroz S M Silva D Carvalho and F M LancasldquoSolid-phase microextraction-liquid chromatography (SPME-LC) determination of lamotrigine simultaneously with carba-mazepine and carbamazepine 10 11-epoxide in human plasmardquoJournal of Se-Paration Science vol 25 no 1-2 pp 91ndash95 2002

[41] C Fernandes A J D SNeto J C Rodrigues CAlves and FMLancas ldquoSolid-phase microextraction-liquid chromatography(SPME-LC) determination of fluoxetine and norfluoxetine inplasma using a heated liquid flow through interfacerdquo Journal ofChromatography B vol 847 no 2 pp 217ndash223 2007

[42] M Katayama Y I Matsuda K Shimokawa et al ldquoDetermina-tion of 120573-blockers by high performance liquid chromatographycoupled with solid phase microextraction from urine andplasma samplesrdquo Analytical Letters vol 34 no 1 pp 91ndash1012001

[43] C Alves C Fernandes A J D S Neto J C RodriguesM E C Queiroz and F M Lancas ldquoOptimization of theSPME parameters and its online coupling with HPLC for theanalysis of tricyclic antidepressants in plasma samplesrdquo Journalof Chromatographic Science vol 44 no 4 pp 340ndash364 2006

[44] A Aresta F Palmisano and C G Zambonin ldquoDeterminationof naproxen in human urine by solid-phase microextractioncoupled to liquid chromatographyrdquo Journal of Pharmaceuticaland Biomedical Analysis vol 39 no 3-4 pp 643ndash647 2005

[45] J A Caris A R Chaves and M E C Queiroz ldquoEvaluationof solid-phase microextraction using a polythiophene filmand liquid chromatography with spectrophotometric detectionfor the determination of antidepressants in plasma samplesrdquoJournal of the Brazilian Chemical Society vol 23 no 1 pp 57ndash64 2012

[46] A R Chaves G C Junior and M E C Queiroz ldquoSolid-phasemicroextraction using poly(pyrrole) film and liquid chro-matography with UV detection for analysis of antidepressantsin plasma samplesrdquo Journal of Chromatography B vol 877 no7 pp 587ndash593 2009

[47] B Bojko D Vuckovic E Cudjoe et al ldquoDetermination oftranexamic acid concentration by solid phase microextractionand liquid chromatography-tandem mass spectrometry firststep to in vivo analysisrdquo Journal of Chromatography B vol 879no 32 pp 3781ndash3787 2011

[48] M D Cantu D R Toso C A Lacerda F M Lancas ECarrilho and M E C Queiroz ldquoOptimization of solid-phasemicroextraction procedures for the determination of tricyclicantidepressants and anticonvulsants in plasma samples by liq-uid chromatographyrdquo Analytical and Bioanalytical Chemistryvol 386 no 2 pp 256ndash263 2006

[49] M E C Queiroz E B Oliveira F Breton and J PawliszynldquoImmunoaffinity in-tube solid phase microextraction coupledwith liquid chromatography-mass spectrometry for analysis offluoxetine in serum samplesrdquo Journal of Chromatography A vol1174 no 1-2 pp 72ndash77 2007

[50] C Alves A J Santos-Neto C Fernandes J C Rodriguesand F M Lancas ldquoAnalysis of tricyclic antidepressant drugsin plasma by means of solid-phase microextraction-liquid


chromatography-mass spectrometryrdquo Journal of Mass Spec-trometry vol 42 no 10 pp 1342ndash1347 2007

[51] W C Davis S S V Pol M M Schantz S E Long R D Dayand S J Christopher ldquoAn accurate and sensitive method forthe determination of methylmercury in biological specimensusing GC-ICP-MS with solid phase microextractionrdquo Journalof Analytical Atomic Spectrometry vol 19 no 12 pp 1546ndash15512004

[52] F Bianchi M Careri M Maffini A Mangia and C MucchinoldquoOptimization of the solid phasemicroextraction procedure forthe ultra-trace determination of organotin compounds by gaschromatography- inductively coupled plasma-mass spectrom-etryrdquo Journal of Analytical Atomic Spectrometry vol 21 no 9pp 970ndash973 2006

[53] L Yang Z Mester and R E Sturgeon ldquoImprovement inmeasurement precision with SPME by use of isotope dilutionmass spectrometry and its application to the determination oftributyltin in sediment using SPME GC-ICP-MSrdquo Journal ofAnalytical Atomic Spectrometry vol 17 no 8 pp 944ndash949 2002

[54] J X Shen C I Tama andRNHayes ldquoEvaluation of automatedmicro solid phase extraction tips (120583-SPE) for the validation of aLC-MSMS bioanalytical methodrdquo Journal of ChromatographyB vol 843 no 2 pp 275ndash282 2006

[55] Z Mester R E Sturgeon and J W Lam ldquoSampling anddetermination ofmetal hydrides by solid phasemicroextractionthermal desorption inductively coupled plasmamass spectrom-etryrdquo Journal of Analytical Atomic Spectrometry vol 15 no 11pp 1461ndash1465 2000

[56] A P Vonderheide M Montes-Bayon and J A Caruso ldquoSolid-phase microextraction as a sample preparation strategy forthe analysis of seleno amino acids by gas chromatography-inductively coupled plasma mass spectrometryrdquo Analyst vol127 no 1 pp 49ndash53 2002

[57] Y-K Tsoi S Tam and K S-Y Leung ldquoRapid speciation ofmethylated and ethylated mercury in urine using headspacesolid phase microextraction coupled to LC-ICP-MSrdquo Journal ofAnalytical Atomic Spectrometry vol 25 no 11 pp 1758ndash17622010

[58] P OlszowyM Szultka T Ligor J Nowaczyk and B BuszewskildquoFibers with polypyrrole and polythiophene phases for isolationand determination of adrenolytic drugs from human plasma bySPME-HPLCrdquo Journal of Chromatography B vol 878 no 24pp 2226ndash2234 2010

[59] A A Rajabi Y Yamini M Faraji and S Seidi ldquoSolid-phasemicroextraction based on cetyltrimethylammonium bromide-coatedmagnetic nanoparticles for determination of antidepres-sants from biological fluidsrdquoMedicinal Chemistry Research vol22 no 4 pp 1570ndash1577 2013

[60] A Aresta L Monaci and C G Zambonin ldquoDetermination ofdelorazepam in urine by solid-phase microextraction coupledto high performance liquid chromatographyrdquo Journal of Phar-maceutical and Biomedical Analysis vol 28 no 5 pp 965ndash9722002

[61] C Deng N Li J Ji B Yang G Duan and X Zhang ldquoDevel-opment of water-phase derivatization followed by solid-phasemicroextraction and gas chromatographymass spectrometryfor fast determination of valproic acid in human plasmardquo RapidCommunications in Mass Spectrometry vol 20 no 8 pp 1281ndash1287 2006

[62] N Unceta A Gomez-Caballero A Sanchez et al ldquoSimulta-neous determination of citalopram fluoxetine and their main

metabolites in human urine samples by solid-phase microex-traction coupled with high-performance liquid chromatogra-phyrdquo Journal of Pharmaceutical and Biomedical Analysis vol 46no 4 pp 763ndash770 2008

[63] R Alizadeh N M Najafi and E M A Poursanic ldquoArraysof SnO

2

nanorods as novel solid phase microextraction fortrace analysis of antidepressant drugs in body fluidsrdquo Journalof Pharmaceutical and Biomedical Analysis vol 70 no 4 pp492ndash498 2012

[64] B Buszewski M Szultka P Olszowy S Bocian and T LigorldquoA novel approach to the rapid determination of amoxicillinin human plasma by solid phase microextraction and liquidchromatographyrdquo Analyst vol 136 no 12 pp 2635ndash2642 2011

[65] P Olszowy M Szultka and B Buszewski ldquoPoly(3-alkylthiophenes) new sorption materials for solid phasemicroextraction of drugs isolated from human plasmardquoAnalytical and Bioanalytical Chemistry vol 401 no 4 pp1377ndash1384 2011

[66] P Olszowy M Szultka J Nowaczyk and B Buszewski ldquoAnew way of solid-phase microextraction fibers preparation forselected antibiotic drug determination by HPLC-MSrdquo Journalof Chromatography B vol 879 no 25 pp 2542ndash2548 2011

[67] A R M de Oliveira and P S Bonato ldquoStereoselective deter-mination of hydroxychloroquine and its major metabolitesin human urine by solid-phase microextraction and HPLCrdquoJournal of Separation Science vol 30 no 15 pp 2351ndash2359 2007


[69] J Wu H Lord H Kataoka and J Pawliszyn ldquoPolypyrrole-coated capillary in-tube solid phase microextraction coupledwith liquid chromatography-electrospray ionizationmass spec-trometry for the determination of 120573-blockers in urine andserum samplesrdquo Journal of Microcolumn Separations vol 12 no4 pp 255ndash266 2000

[70] W M Mullett K Levsen J Borlak J Wu and J PawliszynldquoAutomated in-tube solid-phase microextraction coupled withHPLC for the determination of N-nitrosamines in cell culturesrdquoAnalytical Chemistry vol 74 no 7 pp 1695ndash1701 2002

[71] M Walles W M Mullett K Levsen J Borlak G Wunsch andJ Pawliszyn ldquoVerapamil drugmetabolism studies by automatedin-tube solid phase microextractionrdquo Journal of Pharmaceuticaland Biomedical Analysis vol 30 no 2 pp 307ndash319 2002

[72] K Jinno M Kawazoe Y Saito T Takeichi and M HayashidaldquoSample preparation with fiber-in-tube solid-phase microex-traction for capillary electrophoretic separation of tricyclicantidepressant drugs in human urinerdquo Electrophoresis vol 22no 17 pp 3785ndash3790 2001

[73] L J Yan Q H Zhang Y Q Feng et al ldquoOctyl-functionalizedhybrid silica monolithic column for reversed-phase capillaryelec-trochromatographyrdquo Journal of Chromatography A vol1121 no 1 pp 92ndash98 2006

[74] M M Zheng S T Wang W K Hu and Y Q Feng ldquoIn-tube solid-phase microextraction based on hybrid silica mono-lith coupled to liquid chromatography-mass spectrometry forautomated analysis of ten antidepressants in human urine andplasmardquo Journal of Chromatography A vol 1217 no 48 pp7493ndash7501 2010

[75] R Jarmalaviciene M Szumski O Kornysova et al ldquoCouplingof solid-phase microextraction continuous bed (monolithic)


capillaries with capillary zone electrophoresis for direct analysisof drugs in biological fluidsrdquo Electrophoresis vol 29 no 8 pp1753ndash1760 2008

[76] A R Chaves B J G Silva F M Lancas and M E CQueiroz ldquoBiocompatible in-tube solid phase microextractioncoupled with liquid chromatography-fluorescence detection fordetermination of interferon 120572 in plasma samplesrdquo Journal ofChromatography A vol 1218 no 21 pp 3376ndash3381 2011

[77] S W Zhang J Xing L S Cai and C Y Wu ldquoMolecu-larly imprinted monolith in-tube solid-phase microextractioncoupled with HPLCUV detection for determination of 8-hydroxy-21015840-deoxyguanosine in urinerdquo Analytical and Bioana-lytical Chemistry vol 395 no 2 pp 479ndash487 2009

[78] D L Deng J Y Zhang C Chen X L Hou Y Y Suand L Wu ldquoMonolithic molecular imprinted polymer fiberfor recognition and solid phase microextraction of ephedrineand pseudoephedrine in biological samples prior to capillaryelectrophoresis analysisrdquo Journal of Chromatography A vol1219 pp 195ndash200 2012

[79] W Zhang and Z Chen ldquoMussel inspired polydopamine func-tionalized poly(ether ether ketone) tube for online solid-phasemicroextraction-high performance liquid chromato-graphyand its application in analysis of protoberberine alkaloids inrat plasmardquo Journal of Chromatography A vol 1278 pp 29ndash362013

[80] J Nie M Zhang Y Fan Y Wen B Xiang and Y Q FengldquoBiocompatible in-tube solid-phasemicroextraction coupled toHPLC for the determination of angiotensin II receptor antago-nists in human plasma and urinerdquo Journal of ChromatographyB vol 828 no 1-2 pp 62ndash69 2005

[81] Y Wen Y Fan M Zhang and Y Q Feng ldquoDetermination ofcamptothecin and 10-hydroxycamptothecin in human plasmausing polymer monolithic in-tube solid phase microextrac-tion combined with high-performance liquid chromatographyrdquoAnalytical and Bioanalytical Chemistry vol 382 no 1 pp 204ndash210 2005

[82] F Wei Y Fan M Zhang and Y Q Feng ldquoPoly(methacrylicacid-ethylene glycol dimethacrylate) monolith in-tube solid-phase microextraction applied to simultaneous analysis ofsome amphetamine derivatives in urine by capillary zoneelectrophoresisrdquo Electrophoresis vol 26 no 16 pp 3141ndash31502005

[83] Q W Yu X Wang Q Ma B F Yuan H B He and Y QFeng ldquoAutomated analysis of non-steroidal anti-inflammatorydrugs in human plasma and water samples by in-tube solid-phase microextraction coupled to liquid chromatography-massspectrometry based on a poly(4-vinylpyridine-co-ethylenedimethacrylate) monolithrdquoAnalytical Methods vol 4 no 6 pp1538ndash1545 2012

[84] L P Melo R H C Queiroz and M E C Queiroz ldquoAutomateddetermination of rifampicin in plasma samples by in-tube solid-phase microextraction coupled with liquid chromatographyrdquoJournal of Chromatography B vol 879 no 24 pp 2454ndash24582011

[85] A R Chaves and M E C Queiroz ldquoImmunoaffinity in-tubesolid phase microextraction coupled with liquid chromatogra-phy with fluorescence detection for determination of interferon120572 in plasma samplesrdquo Journal of Chromatography B vol 928 pp37ndash43 2013

[86] J A Caris B J G A Silva E C D Moises V L C Lanchoteand M E N C Queiroz ldquoAutomated analysis of lidocaine andits metabolite in plasma by in-tube solid-phasemicroextraction

coupled with LC-UV for pharmacokinetic studyrdquo Journal ofSeparation Science vol 35 no 5-6 pp 734ndash741 2012

[87] Z Zhang and J Pawliszyn ldquoHeadspace solid-phase microex-tractionrdquo Analytical Chemistry vol 65 no 14 pp 1843ndash18521993

[88] U Staerk andW R Kulpmann ldquoHigh-temperature solid-phasemicroextraction procedure for the detection of drugs by gaschromatography-mass spectrometryrdquo Journal of Chromatogra-phy B vol 745 no 2 pp 399ndash411 2000

[89] S Bigham F Medlar A Kabir C Shende A Alli and AMalikldquoSol-gel capillary microextractionrdquo Analytical Chemistry vol74 no 4 pp 752ndash761 2002

[90] M Spichiger R C Muhlbauer and R Brenneisen ldquoDeter-mination of menthol in plasma and urine of rats andhumans by headspace solid phase microextraction and gaschromatography-mass spectrometryrdquo Journal of Chromatogra-phy B vol 799 no 1 pp 111ndash117 2004

[91] E Turiel J L Tadeo and A Martin-Esteban ldquoMolecularlyimprinted polymeric fibers for solid-phase microextractionrdquoAnalytical Chemistry vol 79 no 8 pp 3099ndash3104 2007

[92] WMMullett P Martin and J Pawliszyn ldquoIn-tubemolecularlyimprinted polymer solid-phase microextraction for the selec-tive determination of propranololrdquo Analytical Chemistry vol73 no 11 pp 2383ndash2389 2001

[93] E H M Koster C Crescenzi W D Hoedt K Ensing and GJ de Jong ldquoFibers coated with molecularly imprinted polymersfor solid-phase microextractionrdquo Analytical Chemistry vol 73no 13 pp 3140ndash3145 2001

[94] X Hua Y Hu and G Li ldquoDevelopment of novel molecularlyimprinted solid-phase microextraction fiber and its applicationfor the determination of triazines in complicated samples cou-pled with high-performance liquid chromatographyrdquo Journal ofChromatography A vol 1147 no 1 pp 1ndash9 2007

[95] D Djozan and T Baheri ldquoPreparation and evaluation of solid-phase microextraction fibers based on monolithic molecularlyimprinted polymers for selective extraction of diacetylmor-phine and analogous compoundsrdquo Journal of ChromatographyA vol 1166 no 1-2 pp 16ndash23 2007

[96] X Hu Y Hu and G Li ldquoPreparation and characterization ofprometryn molecularly imprinted solid-phase microextractionfibersrdquo Analytical Letters vol 40 no 4 pp 645ndash660 2007

[97] F Tan H Zhao X Li et al ldquoPreparation and evaluation ofmolecularly imprinted solid-phase microextraction fibers forselective extraction of bisphenol A in complex samplesrdquo Journalof Chromatography A vol 1216 no 30 pp 5647ndash5654 2009

[98] S Xu X Zhang Y Suna and D Yu ldquoMicrowave-assistedpreparation of monolithic molecularly imprinted polymericfibers for solid phase microextractionrdquo Analyst vol 138 no 2pp 2982ndash2987 2013

[99] L Qiu W Liu M Huang and L Zhang ldquoPreparation andapplication of solid-phase microextraction fiber based onmolecularly imprinted polymer for determination of anabolicsteroids in complicated samplesrdquo Journal of Chromatography Avol 1217 no 40 pp 7461ndash7470 2010

[100] J Huang Y Hu Y Hu and G Li ldquoDevelopment of metalcomplex imprinted solid-phase microextraction fiber for 221015840dipyridine recognition in aqueous mediumrdquo Talanta vol 83 p1721 2011

[101] M Szultka J Szeliga M Jackowski and B Buszewski ldquoDevel-opment of novel molecularly imprinted solid-phase microex-traction fibers and their application for the determination


of antibiotic drugs in biological samples by SPME-LCMSrdquoAnalytical and Bioanalytical Chemistry vol 403 no 3 pp 785ndash796 2012

[102] C Ma H Chen N Sun Y Ye and H Chen ldquoPreparationof molecularly imprinted polymer monolith with an ana-logue of thiamphenicol and application to selective solid-phasemicroextractionrdquo Food Analytical Methods vol 5 no 6 pp1267ndash1275 2012

[103] YHu J PanK ZhangH Lian andG Li ldquoNovel applications ofmolecularly-imprinted polymers in sample preparationrdquo TrACTrends in Analytical Chemistry vol 43 pp 37ndash52 2013

[104] T Hyotylainen and M-L Riekkola ldquoSorbent- and liquid-phasemicroextraction techniques and membrane-assisted extractionin combination with gas chromatographic analysis a reviewrdquoAnalytica Chimica Acta vol 614 no 1 pp 27ndash37 2008

[105] M Kawaguchi R Ito K Saito andHNakazawa ldquoNovel stir barsorptive extraction methods for environmental and biomedicalanalysisrdquo Journal of Pharmaceutical and Biomedical Analysisvol 40 no 3 pp 500ndash508 2006

[106] W Liu H Wang and Y Guan ldquoPreparation of stir barsfor sorptive extraction using sol-gel technologyrdquo Journal ofChromatography A vol 1045 no 1-2 pp 15ndash22 2004

[107] A Kabir K G Furton and A Malik ldquoInnovations in sol-gelmicroextraction phases for solvent-free sample preparation inanalytical chemistryrdquo TrAC Trends in Analytical Chemistry vol45 pp 197ndash218 2013

[108] C Yu and B Hu ldquoSol-gel polydimethylsiloxanepoly(vin-ylalcohol)-coated stir bar sorptive extraction of organophos-phorus pesticides in honey and their determination by largevolume injection GCrdquo Journal of Separation Science vol 32 no1 pp 147ndash153 2009

[109] C Yu X Li and B Hu ldquoPreparation of sol-gel polyethyleneglycolpolydimethylsiloxane-poly(vinyl alcohol)-coated sorp-tive bar for the determination of organic sulfur compounds inwaterrdquo Journal of Chromatography A vol 1202 no 1 pp 102ndash106 2008

[110] Y Hu Y Zheng F Zhu and G Li ldquoSol-gel coatedpolydimethylsiloxane120573-cyclodextrin as novel stationary phasefor stir bar sorptive extraction and its application to analysis ofestrogens and bisphenol Ardquo Journal of Chromatography A vol1148 no 1 pp 16ndash22 2007

[111] C Yu and B Hu ldquoNovel combined stir bar sorptive extractioncoupled with ultrasonic assisted extraction for the determina-tion of brominated flame retardants in environmental samplesusing high performance liquid chromatographyrdquo Journal ofChromatography A vol 1160 no 1-2 pp 71ndash80 2007

[112] A Martin-Esteban ldquoMolecularly-imprinted polymers as a ver-satile highly selective tool in sample preparationrdquo TrAC Trendsin Analytical Chemistry vol 45 pp 169ndash181 2013

[113] Z Xu Y Hu Y Hu and G Li ldquoInvestigation of ractopaminemolecularly imprinted stir bar sorptive extraction and its appli-cation for trace analysis of 120573

2

-agonists in complex samplesrdquoJournal of Chromatography A vol 1217 no 22 pp 3612ndash36182010

[114] Y Hu J Li Y Hu and G Li ldquoDevelopment of selective andchemically stable coating for stir bar sorptive extraction bymolecularly imprinted techniquerdquo Talanta vol 82 no 2 pp464ndash470 2010

[115] Y Hu J Li and G Li ldquoSynthesis and application of a novelmolecularly imprinted polymer-coated stir bar formicroextrac-tion of triazole fungicides in soilrdquo Journal of Separation Sciencevol 34 no 10 pp 1190ndash1197 2011

[116] Z Xu C Song Y Hu and G Li ldquoMolecularly imprinted stirbar sorptive extraction coupled with high performance liquidchromatography for trace analysis of sulfa drugs in complexsamplesrdquo Talanta vol 85 no 1 pp 97ndash103 2011

[117] E Turiel and A Martin-Esteban ldquoMolecularly imprinted stirbars for selective extraction of thiabendazole in citrus samplesrdquoJournal of Separation Science vol 35 no 21 pp 2962ndash29692012

[118] X Huang and D Yuan ldquoPreparation of stir bars for sorptiveextraction based onmonolithicmaterialrdquo Journal of Chromatog-raphy A vol 1154 no 1-2 pp 152ndash157 2007

[119] X Huang N Qiu D Yuan and B Huang ldquoA novel stirbar sorptive extraction coating based on monolithic materialfor apolar polar organic compounds and heavy metal ionsrdquoTalanta vol 78 no 1 pp 101ndash106 2009

[120] X Huang J Lin D Yuan and R Hu ldquoDetermination of steroidsex hormones in wastewater by stir bar sorptive extractionbased on poly(vinylpyridine-ethylene dimethacrylate) mono-lithic material and liquid chromatographic analysisrdquo Journal ofChromatography A vol 1216 no 16 pp 3508ndash3511 2009

[121] MA SaracinoG Lazzara B Prugnoli andMA Raggi ldquoRapidassays of clozapine and its metabolites in dried blood spots byliquid chromatography and microextraction by packed sorbentprocedurerdquo Journal of Chromatography A vol 1218 no 16 pp2153ndash2159 2011

[122] L Somaini M A Saracino C Marcheselli S Zanchini GGerra and M A Raggi ldquoCombined liquid chromatography-coulometric detection and microextraction by packed sorbentfor the plasma analysis of long acting opioids in heroin addictedpatientsrdquo Analytica Chimica Acta vol 702 no 2 pp 280ndash2872011

[123] H Vlckova M Rabatinova A Miksova et al ldquoDeterminationof pravastatin and pravastatin lactone in rat plasma and urineusingUHPLC-MSMSandmicroextraction by packed sorbentrdquoTalanta vol 90 pp 22ndash29 2012

[124] R Said A Pohanka M Abdel-Rehim and O Beck ldquoDetermi-nation of four immunosuppressive drugs in whole blood usingMEPS and LC-MSMS allowing automated sample work-upand analysisrdquo Journal of Chromatography B vol 897 pp 42ndash492012

[125] M A Saracino K Tallarico and M A Raggi ldquoLiquid chro-matographic analysis of oxcarbazepine and its metabolites inplasma and saliva after a novel microextraction by packedsorbent procedurerdquo Analytica Chimica Acta vol 661 no 2 pp222ndash228 2010

[126] S Rani and A K Malik ldquoA novel microextraction by packedsorbent-gas chromatography procedure for the simultaneousanalysis of antiepileptic drugs in human plasma and urinerdquoJournal of Separation Science vol 35 no 21 pp 2970ndash2977 2012

[127] M Rodrigues G Alvesc M Rocha J Queiroz and A Fal-cao ldquoFirst liquid chromatographic method for the simulta-neous determination of amiodarone and desethylamiodaronein human plasma using microextraction by packed sorbent(MEPS) as sample preparation procedurerdquo Journal of Chro-matography B vol 913 pp 90ndash91 2013

[128] M A Saracino C Marcheselli L Somaini et al ldquoA noveltest using dried blood spots for the chromatographic assay ofmethadonerdquo Analytical and Bioanalytical Chemistry vol 404no 2 pp 503ndash511 2012

[129] D Oppolzer I Moreno B da Fonseca et al ldquoAnalyticalapproach to determine biogenic amines in urine usingmicroex-traction in packed syringe and liquid chromatography coupled


to electrochemical detectionrdquo Biomedical Chromatography vol27 no 5 pp 608ndash614 2013

[130] S Matysik and F M Matysik ldquoMicroextraction by packed sor-bent coupled with gas chromatographymdashmass spectrometryapplication to the determination of metabolites of monoter-penes in small volumes of human urinerdquo Microchimica Actavol 166 no 1-2 pp 109ndash114 2009

[131] A El-Beqqali A Kussak L Blomberg and M Abdel-Rehim ldquoMicroextraction in packed syringeliquid chromatog-raphyelectrospray tandem mass spectrometry for quantifi-cation of acebutolol and metoprolol in human plasma andurine samplesrdquo Journal of Liquid Chromatography and RelatedTechnologies vol 30 no 4 pp 575ndash586 2007

[132] M Abdel-Rehim Z Hassan P Skansem and M HassanldquoSimultaneous determination of busulphan in plasma samplesby liquid chromatography-electrospray ionization mass spec-trometry utilizing microextraction in packed syringe (MEPS)as on-line sample preparation methodrdquo Journal of LiquidChromatography and Related Technologies vol 30 no 20 pp3029ndash3041 2007

[133] M Szultka R Krzeminski J Szeliga M Jackowski and BBuszewski ldquoA new approach for antibiotic drugs determi-nation in human plasma by liquid chromatography massmdashspectrometryrdquo Journal of Chromatography A vol 1272 pp 41ndash49 2013

[134] F Lafay E Vulliet andMM Flament-Waton ldquoContribution ofmicroextraction in packed sorbent for the analysis of cotininein human urine by GC-MSrdquo Analytical and BioanalyticalChemistry vol 396 no 2 pp 937ndash941 2010

[135] R Wietecha-Posłuszny A Garbacik M Wozniakiewicz AMoos M Wieczorek and P Koscielniak ldquoApplication ofmicroextraction by packed sorbent to isolation of psychotropicdrugs from human serumrdquo Analytical and Bioanalytical Chem-istry vol 402 no 7 pp 2249ndash2257 2012

[136] B M da Fonseca I E D Moreno M Barroso S Costa J AQueiroz and E Gallar-do ldquoDetermination of seven selectedantipsychotic drugs in human plasma using microextractionin packed sorbent and gas chromatography-tandemmass spec-trometryrdquo Analytical and Bioanalytical Chemistry vol 405 no12 pp 3953ndash3963 2013

[137] Z Altun M Abdel-Rehim and L G Blomberg ldquoNew trends insample preparation on-line microextraction in packed syringe(MEPS) for LC and GC applicationsmdashpart III determinationand validation of local anaesthetics in human plasma samplesusing a cation exchange sorbent and MEPS-LC-MS-MSrdquo Jour-nal of Chromatography B vol 813 no 1-2 pp 129ndash135 2004

[138] M Abdel-Rehim M Dahlgren and L Blomberg ldquoQuantifica-tion of ropivacaine and its major metabolites in human urinesamples utilizing microextraction in a packed syringe auto-mated with liquid chromatography-tandemmass spectrometry(MEPS-LC-MSMS)rdquo Journal of Separation Science vol 29 no11 pp 1658ndash1661 2006

[139] Z Altun L Blomberg E Jagerdeo and M Abdel-RehimldquoDrug screening using microextraction in a packed syringe(MEPS)mass spectrometry utilizing monolithic- polymer-and silica-based sorbentsrdquo Journal of Liquid Chromatographyand Related Technologies vol 29 no 6 pp 829ndash839 2006

[140] A R Chaves F Z Leandro J A Carris and M E CQueiroz ldquoMicroextraction in packed sorbent for analysis ofantidepressants in human plasma by liquid chromatographyand spectrophotometric detectionrdquo Journal of ChromatographyB vol 878 no 23 pp 2123ndash2129 2010

[141] M Abdel-Rehim M Dahlgren L Blomberg S Claude andR Tabacchi ldquoMicroextraction in packed syringe (MEPS) uti-lizing methylcyanopropylsilarylene as coating polymer forextraction of drugs in biological samplesrdquo Journal of LiquidChromatography and Related Technologies vol 29 no 17 pp2537ndash2544 2006

[142] MAbdel-Rehim L I Andersson Z Altun and LG BlombergldquoIncreasing sample preparation throughput using monolithicmethacrylate polymer as packing material for 96-tip roboticdevicerdquo Journal of Liquid Chromatography and Related Tech-nologies vol 29 no 12 pp 1725ndash1736 2006

[143] R Said Z Hassan M Hassan and M Abdel-Rehim ldquoRapidand sensitive method for determination of cyclophosphamidein patients plasma samples utilizing microextraction by packedsorbent online with liquid chromatography-tandemmass spec-trometry (MEPS-LC-MSMS)rdquo Journal of Liquid Chromatogra-phy and Related Technologies vol 31 no 5 pp 683ndash694 2008

[144] E Candish A Gooley H J Wirth P A Dawes R A Shellieand E F Hilder ldquoA simplified approach to direct SPE-MSrdquoJournal of Separation Science vol 35 no 18 pp 2399ndash24062012

[145] K Nielsen F R Lauritsen T Nissila and R A Ketola ldquoRapidscreening of drug compounds in urine using a combinationof microextraction by packed sorbent and rotating micropillararray electrospray ionization mass spectrometryrdquo Rapid Com-munications in Mass Spectrometry vol 26 no 3 pp 297ndash3032012

[146] M Abdel-Rehim ldquoMicroextraction by packed sorbent (MEPS)a tutorialrdquo Analytica Chimica Acta vol 701 no 2 pp 119ndash1282011

[147] S M Daryanavard A Jeppsson-Dadoun L I AnderssonM Hashemi A Colmjso and M Abdel-Rehim ldquoMolecularlyimprinted polymer in microextraction by packed sorbent forthe simultaneous determination of local anesthetics lidocaineropivacaine mepivacaine and bupivacaine in plasma and urinesamplesrdquo Biomedical Chromatography vol 27 no 11 pp 1481ndash1488 2013

[148] N Y Ashri M Daryanavard and M Abdel-Rehim ldquoMicroex-traction by packed sorbent and liquid chromatography-tandemmass spectrometry as a tool for quantification of peptidesin plasma samples determination of sensory neuron-specificreceptors agonist BAM8-22 and antagonist BAM22-8 in plasmasamplesrdquo Biomedical Chromatography vol 27 no 3 pp 396ndash403 2013

[149] A Abdel-Rehim and M Abdel-Rehim ldquoScreening and deter-mination of drugs in human saliva utilizing microextractionby packed sorbent and liquid chromatography-tandem massspectrometryrdquo Biomedical Chromatography vol 27 no 9 pp1188ndash1191 2013

[150] M Abdel-Rehim A Andersson A Breitholtz-Emanuelsson etal ldquoMEPS as a rapid sample preparation method to handleunstable compounds in a complex matrix determination ofAZD3409 in plasma samples utilizingMEPS-LC-MS-MSrdquo Jour-nal of Chromatographic Science vol 46 no 6 pp 518ndash523 2008

[151] R Said A Pohanka M Andersson O Beck and M Abdel-Rehim ldquoDetermination of remifentanil in human plasma byliquid chromatography-tandem mass spectrometry utilizingmicro extraction in packed syringe (MEPS) as sample prepara-tionrdquo Journal of Chromatography B vol 879 no 11-12 pp 815ndash818 2011

[152] M Abdel-Rehim Y Askemark C Norsten-Hoog K J Petters-son and M Halldin ldquoQuantification of 4-OH-26-xylidine and


its conjugates in human urine samples utilisingmicroextractionin packed syringe on-line with liquid chromatography andelectrospray tandem mass spectrometry (MEPS-LC-MSMS)rdquoJournal of Liquid Chromatography and Related Technologies vol29 no 16 pp 2413ndash2424 2006

[153] R Said M Kamel A El-Beqqali and M Abdel-RehimldquoMicroextraction by packed sorbent for LC-MSMS determina-tion of drugs in whole blood samplesrdquo Bioanalysis vol 2 no 2pp 197ndash205 2010

[154] Z Altun L G Blomberg and M Abdel-Rehim ldquoIncreasingsample preparation throughput using monolithic methacrylatepolymer as packing material for 96-tip robotic devicerdquo Journalof Liquid Chromatography and Related Technologies vol 29 no10 pp 1477ndash1489 2006

[155] Z Altun A Hjelmstrom L G Blomberg and M Abdel-Rehim ldquoEvaluation of monolithic packed 96-tips for solid-phase extraction of local anesthetics from human plasma forquantitation by liquid chromatography tandemmass spectrom-etryrdquo Journal of Liquid Chromatography and Related Technolo-gies vol 31 no 5 pp 743ndash751 2008

[156] Z Altun AHjelmstromMAbdel-Rehim and L G BlombergldquoSurface modified polypropylene pipette tips packed with amonolithic plug of adsorbent for high-throughput samplepreparationrdquo Journal of Separation Science vol 30 no 12 pp1964ndash1972 2007

[157] M Abdel-Rehim C Persson Z Altun and L BlombergldquoEvaluation of monolithic packed 96-tips and liquidchromatography-tandemmass spectrometry for extraction andquantification of pindolol and metoprolol in human plasmasamplesrdquo Journal of Chromatography A vol 1196-1197 no 1-2pp 23ndash27 2008

[158] Z Altun C Skoglund and M Abdel-Rehim ldquoMonolithicmethacrylate packed 96-tips for high throughput bioanalysisrdquoJournal of Chromatography A vol 1217 no 16 pp 2581ndash25882010

[159] C Skoglund F Bassyouni and M Abdel-Rehim ldquoMonolithicpacked 96-tips set for high-throughput sample preparationdetermination of cyclophosphamide and busulfan in wholeblood samples by monolithic packed 96-tips and LC-MSrdquoBiomedical Chromatogrphy vol 27 no 6 pp 714ndash719 2013

[160] J Liu K Hara S Kashimura T Hamanaka S Tomojiri and KTanaka ldquoGas chromatographic-mass spectrometric analysis ofdichlorobenzene isomers in humanbloodwith headspace solid-phase microextractionrdquo Journal of Chromatography B vol 731no 2 pp 217ndash221 1999

[161] C Kohlert G Abel E Schmid and M Veit ldquoDeterminationof thymol in human plasma by automated headspace solid-phase microextraction-gas chromatographic analysisrdquo Journalof Chromatography B vol 767 no 1 pp 11ndash18 2002

[162] A Namera M Yashiki and T Kojima ldquoAutomated headspacesolid-phase microextraction and in-matrix derivatization forthe determination of amphetamine-related drugs in humanurine by gas chromatography-mass spectrometryrdquo Journal ofChromatographic Science vol 40 no 1 pp 19ndash25 2002

[163] Y Sha C Deng Z Liu T Huang B Yang and GDuan ldquoHeadspace solid-phase microextraction and capillarygas chromatographic-mass spectrometric determination ofrivastigmine in canine plasma samplesrdquo Journal of Chromatog-raphy B vol 806 no 2 pp 271ndash276 2004

[164] C Deng S Lin T Huang G Duan and X Zhang ldquoDevel-opment of gas chromatographymass spectrometry followingheadspace solid-phase microextraction for fast determination

of asarones in plasmardquo Rapid Communications in Mass Spec-trometry vol 20 no 14 pp 2120ndash2126 2006

[165] L Dong C Deng J Wang and X Shen ldquoFast determinationof paeonol in plasma by headspace solid-phasemicroextractionfollowed by gas chromatography-mass spectrometryrdquoAnalyticaChimica Acta vol 585 no 1 pp 76ndash80 2007

[166] H Bagheri A Es-haghi F Khalilian andM R Rouini ldquoDeter-mination of fentanyl in human plasma by head-space solid-phase microextraction and gas chromatography-mass spec-trometryrdquo Journal of Pharmaceutical and Biomedical Analysisvol 43 no 5 pp 1763ndash1768 2007

[167] M Xu A V Terry J Bartlett and M G Bartlett ldquoDeter-mination of diisopropylfluorophosphate in rat plasma andbrain tissue by headspace solid-phase microextraction gaschromatographymass spectrometryrdquo Rapid Communicationsin Mass Spectrometry vol 22 no 17 pp 3069ndash3075 2008

[168] N Shinmen X P Lee T Kumazawa et al ldquoSimultaneousdetermination of some phenothiazine derivatives in humanblood by headspace solid-phase microextraction and gas chro-matography with nitrogen-phosphorus detectionrdquo Journal ofAssociation of Official Analytical Chemists International vol 91no 6 pp 1354ndash1362 2008

[169] H Ebrahimzadeh A Mehdinia F Kamarei and E MoradildquoA sensitive method for the determination of methadone inbiological samples using nano-structured 120572-carboxy polypyrrolas a sorbent of SPMErdquo Chromatographia vol 75 no 3-4 pp149ndash155 2012

[170] J N Matlow K Aleksa A Lubetsky and G Koren ldquoThe detec-tion and quantification of ethyl glucuronide in placental tissueand placental perfusate by headspace solid-phase microextrac-tion coupled with gas chromatography-mass spectrometryrdquoCanadian Journal of Clinical Pharmacology vol 19 no 3 pp473ndash482 2012

[171] M Jamrogiewicz and BWielgomas ldquoDetection of some volatiledegradation products released during photoexposition of rani-tidine in a solid staterdquo Journal of Pharmaceutical and BiomedicalAnalysis vol 76 pp 177ndash182 2013

[172] C L Silva and J S Ccmara ldquoProfiling of volatiles in the leavesof Lamiaceae species based on headspace solid phase microex-traction and mass spectrometryrdquo Food Research Internationalvol 51 no 1 pp 378ndash387 2013

[173] S M Z Zakir Hossain B Bojko and J Pawliszyn ldquoSilica-based ionic liquid coating for 96-blade system for extraction ofaminoacids from complex matrixesrdquo Analytica Chimica Actavol 776 pp 41ndash49 2013

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


(MEPS) MEPS is the miniaturization of conventional SPEand can be connected online to GC or LC without anymodifications [18ndash22] The extraction steps in MEPS are thesame as in standard SPEmdashextraction loading washing andelutionmdashand these have to be optimized to obtain the highestanalyte recovery In MEPS solvent and sample volumes aresignificantly reduced compared to SPETheMEPS techniquehas beenused to extract awide range of drugs andmetabolitesin biological fluids such as urine plasma and blood [22]

This review presents recent developments of sample prep-aration in drug bioanalysis of complex fluids using SPMESBSE and MEPS

2 Solid Phase Microextraction (SPME) forDrug Analysis

In SPME the extraction is based on the partitioning of theanalyte between the organic phase on the fused silica fibreand the matrix Many factors such as pH temperature saltconcentration and stirring affect the equilibrium constantand the equilibration time [1] Fibre lifetime is a significantissue SPME fibre is quite sensitive to complex matrix such asplasma In addition type of polymer temperature durationand additives coming from the sample solution influence thestability of the coating It should be noted that additives suchas sodium hydroxide and salt could catalyse polymer thermaldegradation In some bioanalytical studies fibre life-time wasdecreased to about 20 samplings instead of 80 [8 9] In thetwo past decades SPME as a sample preparation method fordrug analysis has been used with various analysis methodsSPME was used with different separation techniques suchas capillary gas chromatography (CGC) [23ndash30] GCGC-MS [31ndash37] LCLC-MS [38ndash50] GC-ICP-MS [51ndash57] andHPLC-UVHPLC-MS [58ndash68]

21 Fiber and Monolithic In-Tube SPME In tube solid phasemicroextraction (in-tube SPME) is a new format of SPMEthat can be coupled online to LC for automated analysisof less volatile and polar compounds like drug metabolitesThis technique was used for the determination of drugs andmetabolites in different biological matrices like urine plasmaand cell culture media from in vitro assays [69ndash71] In addi-tion fiber in-tube SPME online with capillary electrophoresis(CE) was used for the analysis of amitriptyline imipraminenortriptyline and desipramine in human urine samples [72]In this work two types of Zylon fiber were used One ishigh modulus (HM) with heat treatment and the other isregular (AS) without heat treatment after spinning the fibersIn addition DB-5 capillary of 10mm length was packed witha fiber with the same length In order to investigate theeffect of the fiber and the capillary coating on extractionefficiency various kinds of extraction media were preparedas follows HM fiber packed in a DB-5 capillary HMDB-5 AS fiber packed in a DB-5 capillary ASDB-5 HM fiberpacked in an uncoated fused-silica capillary HMFS andonly DB-5 capillary DB-5 For the evaluation of the effectof the packing density on the extraction efficiency 26 and52 packed capillaries were prepared The packing density

has been calculated by using the average diameter of the fibersas 115 120583m The former was packed with 123 filaments andthe latter with 246 filaments in a 10mm DB-5 capillary [72]This method was then applied to the analysis of amitriptylinein human urine and the results showed that the hyphenatedsystem would be a powerful tool for the analysis of analytesin biological matrices DB-5 capillary was cut to 10mmlength and the fiber of the same length was packed intothis capillary In order to investigate the effect of the fiberand the capillary coating on extraction efficiency variouskinds of extractionmedia were prepared as follows HM fiberpacked in a DB-5 capillary HMDB-5 AS fiber packed in aDB-5 capillary ASDB-5 HM fiber packed in an uncoatedfused-silica capillary HMFS and only DB-5 capillary DB-5 For the evaluation of the effect of the packing density onthe extraction efficiency 26 and 52 packed capillaries wereprepared The packing density has been calculated by usingthe average diameter of the fibers as 115 120583mThe former waspacked with 123 filaments and the latter with 246 filaments ina 10mm DB-5 capillary The density is based on the volumeratio between the space and the filled part of the innercapillary in which the fibers were packedThe running bufferwas composed of 20mMNa2HPO4 buffer (pH 93) 06mM-cyclodextrin and 20 acetonitrile

Monolith in-tube SPME is another approach for druganalysis in complex matrix Different strategies were devel-oped for preparation of monolithic in tube SPME (Figure 1)A hybrid organic-inorganic silica monolith with ceyanoethylfunctional groups was synthesized by hydrolysis and poly-condensation of precursors via a two-step catalytic sol-gelprocess that was used as a sorbent for in-tube SPME [73 74]Briefly fused-silica capillaries (ID 250 120583m) were activatedwith 1M NaOH and then 1M HCl After rinsing with doubledistilled water they were dried at 160∘C under N

2flow

for 5 h The hybrid monolith was synthesized by hydrolysisand polycondensation of precursors via a two-step catalyticsol-gel process The optimal preparation conditions were asfollows 180 120583L of methanol 25120583L of 2M acetic acid 110 120583Loff CN-TEOS and 110 120583L of TEOS were mixed in a 15mLEppendorf vial After thorough vortexing the mixture wasleft for hydrolysis at 60∘C for 5 h After cooling to roomtemperature 10mg of N-dodecylamine was added to thesolution Then the pretreated capillary was filled to a certainlength with the sol by a syringe The capillary was sealedat both ends with silicone rubber and then was allowed tofurther react at 40∘C for 15 h Subsequently the capillarywas rinsed with ethanol to remove the N-dodecylamine andsoluble hydrolysis products and then dried at 60∘C for 48 hThe total and effective lengths of the hybrid silica monolithwere 20 and 15 cm respectively [74]

As it is shown in Figure 1 four capillaries are connected inthemodified cross connector to build the online fiber-in-tubeSPME-CE system To minimize the band broadening effectsthe gap between the separation capillaries must be strictlydecreased Therefore the capillaries between the two bufferreservoirs were connected using a microscope until the gapbetween the capillaries was less than 10 120583m In addition theSEM picture (Figure 1) showed that the monolith is attached


Sample

Autosampler

Waste

Waste

Valve A

Pump A

Pump B

LC column


MS

Carriersolution

Mobilephase

Load position

Workstation

Inject position

loop

Valve Bemitter

(a)

(b) (c)






Analytical column

Fluorescence

RAM-BSA

Mobile phase

Mobile phase

Position A

To waste

Injection

Position B

detector

















Cut


with a blade5cm

1cm

60∘C24h

30 cm capillary

1120583m

100120583m

(a)

(b)

(c)

20kV times15000

20kV times150










NH2

OHOH

OHOH

OH OH

OHOH

2H+ + 2e 2H+ + 2e

Rearrangement

RearrangementHN

HN HN

Oxidation Oxidation

HO HO


HN

n

(a)

NH2

NH2

NH2

OH

OH

OH

OH

OH

OH

OH

OH

OH

OO

O

OO

OO

O

O

OO

O

O

O O

O

O

OSi

Si

Si

Dopamine

Tris-HCl

EGDMA AA AIBN

Polymerization

(A) (B) (C)

(b)





Plunger

Stopper



Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

















Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Sample

Autosampler

Waste

Waste

Valve A

Pump A

Pump B

LC column


MS

Carriersolution

Mobilephase

Load position

Workstation

Inject position

loop

Valve Bemitter

(a)

(b) (c)






Analytical column

Fluorescence

RAM-BSA

Mobile phase

Mobile phase

Position A

To waste

Injection

Position B

detector

















Cut


with a blade5cm

1cm

60∘C24h

30 cm capillary

1120583m

100120583m

(a)

(b)

(c)

20kV times15000

20kV times150










NH2

OHOH

OHOH

OH OH

OHOH

2H+ + 2e 2H+ + 2e

Rearrangement

RearrangementHN

HN HN

Oxidation Oxidation

HO HO


HN

n

(a)

NH2

NH2

NH2

OH

OH

OH

OH

OH

OH

OH

OH

OH

OO

O

OO

OO

O

O

OO

O

O

O O

O

O

OSi

Si

Si

Dopamine

Tris-HCl

EGDMA AA AIBN

Polymerization

(A) (B) (C)

(b)





Plunger

Stopper



Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

















Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Analytical column

Fluorescence

RAM-BSA

Mobile phase

Mobile phase

Position A

To waste

Injection

Position B

detector

















Cut


with a blade5cm

1cm

60∘C24h

30 cm capillary

1120583m

100120583m

(a)

(b)

(c)

20kV times15000

20kV times150










NH2

OHOH

OHOH

OH OH

OHOH

2H+ + 2e 2H+ + 2e

Rearrangement

RearrangementHN

HN HN

Oxidation Oxidation

HO HO


HN

n

(a)

NH2

NH2

NH2

OH

OH

OH

OH

OH

OH

OH

OH

OH

OO

O

OO

OO

O

O

OO

O

O

O O

O

O

OSi

Si

Si

Dopamine

Tris-HCl

EGDMA AA AIBN

Polymerization

(A) (B) (C)

(b)





Plunger

Stopper



Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

















Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




Cut


with a blade5cm

1cm

60∘C24h

30 cm capillary

1120583m

100120583m

(a)

(b)

(c)

20kV times15000

20kV times150










NH2

OHOH

OHOH

OH OH

OHOH

2H+ + 2e 2H+ + 2e

Rearrangement

RearrangementHN

HN HN

Oxidation Oxidation

HO HO


HN

n

(a)

NH2

NH2

NH2

OH

OH

OH

OH

OH

OH

OH

OH

OH

OO

O

OO

OO

O

O

OO

O

O

O O

O

O

OSi

Si

Si

Dopamine

Tris-HCl

EGDMA AA AIBN

Polymerization

(A) (B) (C)

(b)





Plunger

Stopper



Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

















Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


NH2

OHOH

OHOH

OH OH

OHOH

2H+ + 2e 2H+ + 2e

Rearrangement

RearrangementHN

HN HN

Oxidation Oxidation

HO HO


HN

n

(a)

NH2

NH2

NH2

OH

OH

OH

OH

OH

OH

OH

OH

OH

OO

O

OO

OO

O

O

OO

O

O

O O

O

O

OSi

Si

Si

Dopamine

Tris-HCl

EGDMA AA AIBN

Polymerization

(A) (B) (C)

(b)





Plunger

Stopper



Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

















Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Plunger

Stopper



Fiber

Solidsample

Septumand cap

Fiberattachment

needle

Vial

Block heater

















Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Table1HSP

MEfora

nalysis

ofdifferent

drug

compo

nents

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Dichlorob

enzene

Dam

agetotheliver

and

thek

idneys


Hum

anbloo

dGCMS

[160]


amph

etam

ine

secobarbita

lph

enob

arbitalmethado

ne

prop


codeineflu

nitrazepam

diacetylated

morph

ine)

Polyacrylate

(Insitu)

deriv

atisa

tion

(acetylatio

nor

silylation)

Urin

eserum

GCMS

[88]

Thym

olFo

odpharm

aceutic

als


divinylbenzene

crim

pedfib

erHum

anplasma

GCMS

[161]

Amph

etam

ine-related

drugs

Abused

drugs


Hum

anurine

GCMS

[162]

Rivastigmine

Symptom

atictre

atment

ofmild

tomod

erate

dementia


(pdm

sdvb)o

rpolydim

ethylsiloxane

(pdm

s)Ca

nine

plasma

GCMS

[163]

Menthol

Flavou

ringagent

65120583m


(PDMSDVB)-coatedfib

ers

Plasmaurineo

frats

GCMS

[90]

Ephedrinemethamph

etam

ine

Anaesthesia

psycho

activ

edrug

Sol-g

elHum

anurine

GC

[34]

Asaron



(PDMS)65120583

mm


(PDMSDVB)65120583

mm

carbow

axdivinylbenzene(

CWD

VB)75120583

mm

carboxen

poly(dim

ethylsiloxane)

(CARPD

MS)

85120583mm

polyacrylate(PA)

Plasma

GCMS

[164

]

Paeono

lEczema

100120583

mpo

lydimethylsiloxane

(PDMS)65120583

mpo


(PDMS-DVB)65120583

mcarbow

axdivinylbenzene(

CW-D

VB)75120583

mcarboxen

poly(dim

ethylsiloxane)

(CAR-PD

MS)and

85120583m

polyacrylate(PA)

were

purchasedfro


USA

)


oil

GCMS

[165]

Fentanyl

Surgicalanalgesia

and

sedatio

nSol-g

eltechno

logy

Hum

anplasma

GCMS

[166]

Diisop

ropylfluo

roph

osph

ate

Miotic

agentin

treatmento

fchron

icglaucoma

65mm


(pdm

sdvb)

Ratp

lasm

abraintissue

GCMS

[167]


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Table1Con

tinued

Drug

Dise

ase

Fibertype

Samplem

atrix

Analytic

almetho

dRe

ference

Somep

heno

thiazine

deriv

atives

Antipsychotics

(major

tranqu

ilizers)

antip

arkinson

ismdrug

santih

istam

inics

100120583

mPD

MS85120583m


mPD

MSdivinylbenzene

(DVB)65120583

mCa

rbow

ax(C

W)DVB

85120583m

stableflex

carboxen


mstableflexDVBCA

RPD

MS

Hum

anbloo

dGCNPD

[168]

Methado

neAnalgesic


Polypyrrole(pp

y-120572-C

OOH)

Plasmaurine

GCFID

[169]

Ethylglucuronide

Prom

ising

biom

arkero


lexpo

sure

100120583

mpo

lydimethylsiloxane

redandblackfib

ers

Hum

anplacenta

GCMS

[170]

Ranitid

ine

Prescribed

Carboxenpolydim

ethylsiloxane

Solid

state

GCMS

[171]

Volatile

organicm

etabolites

volatile

organic

metabolites

Pdmspd

msd

vbcwdvb

Pacarpdm

sanddvbcarpd

ms

Menthatimes

piperitaL

GCqM

S[172]

EcoliBL

21Antim

icrobialagents

Fore

xample100120583

mPD

MS65120583m

DVBPD

MS75120583m

CARPD

MS

and5030120583

mCA

RPD

MSDVB

Cellm

etabolism

GCMS

[173]





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of





OC2H5

OC2H5

OC2H5Si


OCH3

OCH3

OCH3CH2

O

CHCH2 O(CH2)3

PDMS Coating SiOO

CH3 CH3 CH3

CH3 CH3 CH3

( )HO OHm

SiSi


OCH3

OCH3

O

O

OH

7


CH3 CH3 CH3 CH3

CH3

CH3CH3CH3

H3C

H

OOO ( )q

( )r








CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


CH3 CH3 CH3 CH3

CH3CH3

CH3 CH3

CH3

CH3

CH3CH3

CH3 CH3

CH3CH3

CH3

CH3

CH3

CH3 CH3

CH3

CH3

CH3

CH3

CH3CH3CH3CH3

CH3

Si

Si

Si Si Si Si Si

SiSi Si Si

Si Si SiSi

Si Si SiO

O

O

O

O

O

O

O O

O O

O O O O O

O

O

OO

O

O O

O O O O O

O

O

O

(

(

(

( (

(

(

(

)

(OCH3)7

(OCH3)7

(OCH3)7

(OCH3)7

(CH2)3O CH2 OH

)r

)

) )

)q

)r

)q

Si Si

Si Si

CHCH2

(CH2)3O CH2 OHCHCH2

mn

mn


30 cm




3M NH4HF2

Removal of silica






From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


From pump


Meteringpump

Injection loop

Injection needle

Column connectors

Autosampler

WasteLC column


Analyte

Interferents

UV detector


Six-port valve

(a)

From pump

Meteringpump

Injection loop

Injection needle

Autosampler

Waste LC column


UV detector


Six-port valve

(b)







HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


HO HO

HO

C C

C

OH OH

OH

CH3

CH2

CH2

CH2

CH2

CH2

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H2C

H2C

H2C

H2C

H2CSelf-assembly

OO O

OO O

O

O

O

O

O

OO

OOO

O OO

O

O

O

O

OO

OOO

O

O

O

O

O

O

OOO

NH2

NH2

NH2

H3N

H2N

H2N

Si

Si Si Si

Si

Si

Si

SiSi



+

C2H

(a) (b)









CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


CH3 CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3 CH3 CH3

CH3 CH3

CH3

CH3

CH3

CH3CH3

CH3 CH3 CH3

CH3 CH3 CH3 CH3

CH3 CH3 CH3

CH3CH3

CH3

CH3 CH3

CH3 CH3

CH3

H3CO

OCH3

OCH3 +

+

+

+

+H2OH2O hydrolysis




HO

HO

HO HO

HO

OH

OHOH

OH

OH

OH

OH OH

OH

OH

OH OH

OH

OH

OH

OO

OO O O O

O

O

OO

OO

O

OO O

O

OO

O O OOO O

O O

O

CH3OH

( )

( ( (

(((

) )

) )

(

(

)

) )

)

Condensation





Fiber surface

Sol-gel precursor

Si Si

Si Si Si Si



Sim

m

m

m

n

n

n

n

n

n HO






Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Si

Si

Si

Si

SiSi

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

Si

OO

OSi

OO

OO Si O

OO

O

O

O

O

O O O

O

OO

Glass capillary

(1) NaOH

(2) HCl

OH

OH

OH

OH

OH HO

OH

OH

+

+


Si O

OO

O

O

Si O

OO

O

O

Polymerization


Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

Si O

OO

O

O

HN NH

Cl


N N

N HN NH

Cl

N N

N

MAA(monomer)

O O

OH HO

HN NH

Cl

Self-assembly




O O

OH HON N

N

(A)

(B)

(a) (b)

(c) (d)

(C)






















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

















[133]





[137]


[138]



[139]



[141]


[142 147]




[144]


[145]


















6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of














6 Conclusions






References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of





References






































































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of













































2

























































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of












































2












































































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

review article solid phase microextraction and related...

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