analytix 4/2014, proficiency testing - a crticial tool
TRANSCRIPT
Issue 4 • 2014
Analytix
• Proficiency Testing Portal
• NEW Flavor & Fragrance
Standards
• Analytical Standards of
Boswellic Acids
• Environmental Monitoring of
Pharmaceuticals
• Clinical Testing of Hormone
Levels
• Solvents for MS Applications
• Carbonate-selective Sensors
Proficiency Testing – A Critical Tool
22
Proficiency Testing – A Critical Tool
sigma-aldrich.com/analytix
Ed
ito
ria
l
Dear Colleagues,
Every year billions of measurements are performed at thousands of test-
ing laboratories worldwide. These tests may include stability testing to
ensure the shelf-life of a pharmaceutical product, microbiological test-
ing to ensure the safety of food products or environmental testing to
monitor the quality of drinking water, to mention but a few.
Laboratories have to critically assess their ability to perform these mea-
surements. Inaccurate measurements could lead to potential legal
action and will certainly lead to loss of accredited status, customers and
revenue.
One of the most useful tools available to assess the laboratory’s ability to
perform these measurements is regular participation in a profi ciency
testing program. Profi ciency testing provides an opportunity for labora-
tories to receive an independent appraisal of their data compared
against a reference value and the performance of peer laboratories.
In an eff ort to deliver the best tools to our laboratory customer, we
have developed a new testing portal which can be accessed at
sigma-aldrich.com/proficiencytesting. This portal was designed
with speed and simplicity as the focus, while providing the tools and
features that PT customers need and have come to expect from their
providers. You can read more about the specifics of this new portal
further down in this issue.
To fi nd more information about our profi ciency testing program and to
see the products that Sigma-Aldrich off ers for profi ciency testing please
visit our webpage located at sigma-aldrich.com/profi ciencytesting
Sigma-Aldrich RTC has been operating proficiency testing programs
since 1994 and is an accredited ISO 17043 PT Provider.
Best regards,
Patrick Brumfi eld
Product Manager Profi ciency Testing
Patrick Brumfield
Product Manager Proficiency Testing
Analytix is published fi ve times per year by Sigma-Aldrich Chemie GmbH,
MarCom Europe, Industriestrasse 25, CH-9471 Buchs SG, Switzerland
Publisher: Sigma-Aldrich Marketing Communications Europe
Publication Manager: Michael Jeitziner
Editor: Daniel Vogler
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sigma-aldrich.com/analytix
Feature Article
4 New Data Entry Portal for Proficiency Testing
Standards
5 Flavor & Fragrance Standards
More than 100 NEW Flavor & Fragrance Standards
for the Food and Cosmetic Industry
6 Getting to the Heart of Frankincense
Analytical Standards of Boswellic Acids and Their
Separation
8 Pharmaceutical Environment
Certified Reference Materials for Environmental
Analysis of Pharmaceuticals
10 Short Overview of Sigma-Aldrich’s Isotope
Labeled Pesticide Standards
Internal Standards for Food and Environmental
Analysis
11 Organic TraceCERT® CRMs
The Newest Product Additions to our Organic Neat
Certified Reference Material Portfolio
12 New & Emerging Clinical Testing
Applications: Monitoring Hormone Levels
during Treatment of Pain
Solution CRMs for Corticosteroids, Progestogens
and Other Hormones
Chromatography
14 Choosing the Right Solvent for your
Application
…and Avoiding Signal Suppression in MS
Sensorics
17 A Remarkable Carbonate-Selective
Ionophore for the Determination of
Oceanic Carbon Dioxide Using an Ion-
Selective Electrode
Spectrometry
18 A New Approach for the Detection of Acidic
Pesticides in Water by MS
Increasing the Sensitivity in Pesticide Analysis by
Paired-Ion ESI Detection
Titration
21 Water Determination in Pharmaceutical
Compounds
Karl Fischer Titration with HYDRANAL® Reagents –
Request the new Hydranal Product Line Overview
Brochure
4
New Data Entry Portal for Proficiency Testing
Previous Study Data/Reports
All of your previous study data will be transferred over to the
new system. This will allow for historical trending of results –
a feature that will be available soon on the new portal.
Webinars on the new Portal
A webinar will be off ered to demo the new portal and fi eld
any questions that you might have. If you don’t have the
opportunity to attend the webinar, a copy will be posted
on the homepage to view at your convenience.
Please contact Pat Brumfi eld (pat.brumfi [email protected]) to
sign up for our webinar taking place on Monday, October 20,
2PM Greenwich Mean Time.
Pat Brumfield, Product Manager Proficiency Testing [email protected]
Fe
atu
re A
rtic
le
sigma-aldrich.com/profi ciencytesting
Sigma-Aldrich® introduces our new proficiency-testing
data-entry portal. The new portal can be accessed at
sigma-aldrich.com/proficiencytesting and will be
available in mid-July 2014. This new portal will replace the
data-entry portal located at www.rt-corp.com
The new portal has been streamlined and will off er superior
speed and ease of use.
Sigma-Aldrich committed resources starting in late 2013 to
design a user interface that was effi cient, simple and some-
thing that would meet the evolving needs of the end user.
The result is our new data-entry portal which is easy to
learn, easy to remember and easy to use.
Some of the features of the new Web portal:
• One-click design that is easy to navigate, even for first
time users
• All open studies prominently displayed on the home
screen
• Easily add new personnel/analysts to your lab
• Add accreditors and enter data all on a single page
• Only the applicable methods are displayed in the
method drop-down box
• Easily copy down method/analyst/analysis date to all
analytes in a sample
• Data is actively saved as you report
• A confirmation screen that shows exactly what you have
entered and will be submitted for evaluation
• The ability to import LIMS files rather than manually
entering your results
5
Flavor & Fragrance Standards More than 100 NEW Flavor & Fragrance Standards for the Food and Cosmetic Industry
Eva Katharina Richter, Product Manager Analytical Standards [email protected]
Sigma-Aldrich® provides a broad range of flavor and fra-
grance standards for quality control of food and cosmetic
products. Our large portfolio focuses on analytical standards
for aroma compounds from the “EU positive list of autho-
rized fl avoring substances” (EFSA 10/2012) and the “EU-Reg-
ulation on cosmetic products” (1223/2009). Our selection,
which is continuously growing, includes allergenic com-
pounds and flavor enhancers as well as EU banned sub-
stances. Test your products against our Flavor & Fragrance
Standards to ensure they maintain their high quality! Find an
up-to-date product list of all Flavor & Fragrance Standards
arranged according to their occurrence in food and bever-
ages, by substance classifi cation, and in alphabetical order
at sigma-aldrich.com/fl avor
Cat. No. Brand Description Package Size
67369 Fluka® (−)-Ambroxide 100 mg
91034 Fluka (−)-Caryophyllene oxide 100 mg
54328 Fluka (−)-Globulol 10 mg
43201 Fluka (−)-Isoledene 100 mg
93483 Fluka (+)-Cedrol 100 mg
44889 Fluka (+)-Nootkatone 50 mg
18032 Fluka (1R)-(–)-Myrtenal 1 mL
56699 Fluka (3aR)-(+)-Sclareolide 100 mg
04969 Fluka (S)-(−)-Perillaldehyde 1 mL
04174 Fluka 1-Acetonaphthone 1 mL, 5 mL
75544 Fluka 1-Dodecanol 1 mL, 5 mL
18698 Fluka 1-Methylpyrrole 1 mL, 5 mL
76723 Fluka 1-Penten-3-one 1 mL
50714 Fluka 2,3,5-Trimethylpyrazine 1 mL
43042 Fluka 2,3-Benzofuran 1 mL
42038 Fluka 2,3-Butanediol 250 mg
56931 Fluka 2,6-Diisopropylphenol 1 mL
18478 Fluka 2-Acetonaphthone 100 mg
55752 Fluka 2-Ethoxynaphthalene 100 mg
69530 Fluka 2-Ethylfuran 1 mL, 5 mL
14249 Fluka 2-Furyl methyl ketone 1 mL
18245 Fluka 2'-Hydroxyacetophenone 1 mL
94414 Fluka 2-Methoxybenzaldehyde 100 mg
61904 Fluka 2-Methylbutyraldehyde 100 mg
92015 Fluka 2-Naphthalenethiol 100 mg
14672 Fluka 2-Pentyl butyrate 1 mL
74350 Fluka 2-Picoline 500 mg
44638 Fluka 3-(Methylthio)propionaldehyde 500 mg
92588 Fluka 3,4-Dihydroxybenzaldehyde 100 mg
94415 Fluka 3-Carene 1 mL, 5 mL
43212 Fluka 3-Heptanol 1 mL
04649 Fluka 3-Hexanol 1 mL
93856 Fluka 3-Octanol 1 mL
05339 Fluka 3-Picoline 1 mL
43045 Fluka 3-Pyridinemethanol 1 mL
90034 Fluka 4-Hydroxy-3-methoxycinnamic acid 100 mg
43919 Fluka 4-Methylthiazole 1 mL, 5 mL
67397 Fluka 6-Methyl-5-hepten-2-one 1 mL
07056 Fluka Allyl cinnamate 1 mL
12448 Fluka alpha-Humulene 250 mg
30627 Fluka alpha-Terpineol 100 mg
68518 Fluka Amylamine 1 mL
95054 Fluka Azelaic acid 100 mg
80024 Fluka Benzoin 100 mg
89983 Fluka Benzyl isothiocyanate 500 mg
08900 Fluka Benzyl mercaptan 1 mL
78466 Fluka Benzyl propionate 1 mL, 5 mL
75031 Fluka Butyl anthranilate 1 mL
68119 Fluka Butyl propionate 1 mL, 5 mL
90893 Fluka Butylamine 1 mL, 5 mL
94194 Fluka Butyraldehyde 1 mL
52063 Fluka Cadaverine 1 mL
43646 Fluka Citronellyl acetate 1 mL
49673 Fluka Dibenzyl ether 1 mL, 5 mL
91969 Fluka Diethyl carbonate 1 mL, 5 mL
Cat. No. Brand Description Package Size
49919 Fluka Dimethyl anthranilate 1 mL
68986 Fluka Dimethyl disulfide 1 mL
04011 Fluka Dimethyl malonate 1 mL
95563 Fluka Ethyl 2-trans-4−decadienoate 25 mg
63954 Fluka Ethyl acetoacetate 1 mL
72505 Fluka Ethyl benzoate 1 mL, 5 mL
66761 Fluka Ethyl cinnamate 100 mg
08996 Fluka Ethyl lactate 1 mL
73539 Fluka Ethyl linoleate 1 mL
91224 Fluka Ethyl phenylacetate 1 mL, 5 mL
43348 Fluka Farnesol 1 mL
89985 Fluka gamma-Undecalactone 1 mL
40951 Fluka gamma-Valerolactone 1 mL
61696 Fluka Heptaldehyde 1 mL
59964 Fluka Histamine 100 mg
80725 Fluka Hydrocinnamic acid 100 mg
66010 Fluka Hydroxycitronellal 1 mL
95668 Fluka Isoamyl octanoate 1 mL, 5 mL
94888 Fluka Isobutyl butyrate 1 mL, 5 mL
06755 Fluka Isobutylamine 1 mL
07055 Fluka Isoeugenyl acetate 100 mg
68853 Fluka Isoquinoline 1 mL
49599 Fluka Linalyl acetate 100 mg
07406 Fluka m-Anisaldehyde 1 mL
95401 Fluka Menthone, mixture of isomers 1 mL, 5 mL
41263 Fluka Methyl benzoylformate 1 mL
80835 Fluka Methyl cinnamate 250 mg
52466 Fluka Octanal 1 mL, 5 mL
08066 Fluka Oleyl alcohol 100 mg
92819 Fluka o-Tolualdehyde 1 mL
94666 Fluka p-Anisic acid 100 mg
66962 Fluka Pentyl acetate 1 mL
73747 Fluka Phenethyl acetate 1 mL, 5 mL
30311 Fluka Phenyl acetate 1 mL
92528 Fluka Phenyl disulfide 100 mg
91897 Fluka Phloretin 10 mg
61074 Fluka Propiophenone 1 mL, 5 mL
53646 Fluka Propylamine 1 mL
41423 Fluka p-Tolualdehyde 1 mL
49817 Fluka Pyrrole 1 mL, 5 mL
94517 Fluka Quinoline 1 mL
42993 Fluka Theobromine 100 mg
92358 Fluka Thioanisole 1 mL
03416 Fluka Thymoquinone 100 mg
05549 Fluka trans-2,cis-6-Nonadienal 100 mg
90244 Fluka trans-2-Heptenal 100 mg
07592 Fluka trans-2-Nonenal 1 mL
52464 Fluka trans-2-Octenal 1 mL, 5 mL
94575 Fluka trans-2-Pentenal 1 mL
74103 Fluka Triacetin 1 mL, 5 mL
43103 Fluka Triethyl orthoformate 1 mL, 5 mL
73487 Fluka Triethylamine 1 mL, 5 mL
80139 Fluka Undecanal 1 mL
94490 Fluka δ-Octalactone, mixture of isomers 1 mL, 5 mL
Table 1 NEW Flavor & Fragrance Standards
sigma-aldrich.com/fl avor
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6S
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sigma-aldrich.com/medicinalplants
are a group of pentacyclic triterpene acids of which
-boswellic acids are the major biologically active constitu-
ents. Sigma Aldrich® off ers six boswellic acids as analytical
standards and two neat standards of + mixtures for use
in research and quality control.
Figure 2 shows the chromatograms of the ethanolic
extract of a boswellia herbal supplement as well as of a
mixture of the six analytical standards.
Getting to the Heart of Frankincense Analytical Standards of Boswellic Acids and Their Separation
The trees of the genus boswellia have been used in tradi-
tional medicine for thousands of years as an anti-infl amma-
tory agent. Its resin is known as frankincense or olibanum
and is still widely used in dietary supplements and in herbal
medicinal products. The most characteristic components
Matthias Nold, Product Manager Analytical Standards [email protected]
Hugh Cramer, Application Scientist [email protected]
06813
-boswellic acid
74607
3-O-Acetyl-11-keto- -boswellic acid
49873
3-O-Acetyl- -boswellic acid
78535
11-keto- -boswellic acid
80342
-boswellic acid
56208
3-O-Acetyl- -boswellic acid
Figure 1 Chemical Structures of the Boswellic Acids
Separation of Boswellic Acids
Several conditions, using a variety of solid phases, have been
screened for their suitability to separate six boswellic acids.
The shortest analysis time was achieved using an Ascentis
Express Column (2.7 μm particle size, L × I.D. 10 cm × 3.0 mm)
and acetonitrile/phosphoric acid as eluents.
HOH3C
OHOH
H3C CH3
CH3
H
H3C CH3
CH3
HOH3C
OHOH
H3C CH3
CH3
H
CH3
H
H3CCH3
H3C
O
OH3C
OHOH
H3C CH3
CH3
H
H3C CH3
CH3
HH3C
O
OH3C
OHOH
H3C CH3
CH3
H
CH3
H
H3CCH3
H3C
O
O
HOH3C
OHOH
H3C CH3
CH3
H
CH3
H
H3CCH3
O
HOH3C
OHOH
H3C CH3
CH3
H
CH3
H
H3CCH3
7
sigma-aldrich.com/medicinalplants
Sta
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A Boswellia Extract
B Analytical Standards at 50 g/mL of Each Component
Conditions
Column: Ascentis Express Phenyl-Hexyl, 10 cm x 3.0 mm I.D., 2.7 μm (53345-U) Mobile Phase: (A) 0.1% phosphoric acid; (B) acetonitrile Gradient: 50% B for 0.5 min; to 100% B in 4.5 min; held at 100% B for 5 min Flow Rate: 0.6 mL/min Pressure: 2390 psi (165 bar) Column temp.: 35 °C Detector: UV at 210 nm Injection: 5 μL Sample(s): 6 Boswellic acids 50μg/mL in 70:30, water:methanol extract in 50:50, water:ethanol Extraction: 1. Weigh 100 mg Bosewellia Herbal Supplement 2. Add 10 mL ethanol 3. Sonicate for 30 min at 40 °C 4. Dilute: 100 μL extract in ethanol, 400 μL ethanol, 500 μL water
Peak IDs
1) 11-Keto-β-boswellic-acid2) 3-O-Acetyl-11-keto-β-boswellic-acid3) α-boswellic-acid4) β-boswellic-acid5) 3-O-Acetyl-α-boswellic-acid6) 3-O-Acetyl-β-boswellic-acid
Figure 2 Experimental Conditions and Chromatograms of the Separation of Boswellic Acids
Cat. No. Brand Description Package Size
74607 Fluka® 3-O-Acetyl-11-keto-β-boswellic acid 5 mg
56208 Fluka 3-O-Acetyl-α-boswellic acid 5 mg
49873 Fluka 3-O-Acetyl-β-boswellic acid 5 mg
96729 Fluka 3-O-Acetylboswellic acid, mixture of α and β 5 mg
06813 Fluka α-Boswellic acid 10 mg
80342 Fluka β-Boswellic acid 5 mg
63850 Fluka Boswellic acid, mixture of α and β 5 mg
78535 Fluka 11-Keto-β-boswellic acid 5 mg
53345-U Supelco® Ascentis Express Phenyl-Hexyl, 2.7 Micron HPLC Column 10 cm × 3.0 mm
Table 1 Analytical Standards of Boswellic Acids and Column Used
Sigma-Aldrich continuously expands its off ering of analytical
standards for plant constituents, intended for the analysis of
medicinal plants and herbal medicinal products.
On our Web page at sigma-aldrich.com/medicinalplants,
you will fi nd an up-to date list of all phytopharma standards
sorted in alphabetical order, by substance class and by
genus of a large number of the most popular medicinal
plants.
8
sigma-aldrich.com/pharmametabolites
Sta
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Therefore, the occurrence and impact of pharmaceutical
substances in the environment is gaining increasing atten-
tion from researchers and authorities, as well as from com-
panies in the pharmaceutical industry, which have an inter-
est in minimizing their ecological footprint. This increasing
attention was also reflected by the huge quantity of ses-
sions and posters on the topic at this year’s SETAC annual
meeting[1]. Many studies support the presumption that
active pharmaceutical substances (API) do have a detrimen-
tal eff ect on the ecosystem and that their release into the
environment needs to be monitored and controlled.
Authorities such as the EPA (U.S. Environmental Protection
Agency)[2] or the German Umweltbundesamt (UBA)[3] per-
form and/or support studies in this field with the aim of
establishing appropriate guidelines. The Water Framework
Directive[4] of the EU also has an eye on pharmaceuticals, and
in 2012, added diclofenac, which was the fi rst pharmaceutical
to be added to the list of proposed priority substances.
Without a doubt, we can attribute our present-day quality
of life and long life expectancy largely to the achievements
of the medical profession during the last century. Nowa-
days, huge quantities of pharmaceutical substances are
produced and consumed. However, either through excre-
tion or improper disposal via the toilet, a lot of pharmaceu-
ticals end up in sewage treatment plants and eventually in
ground and surface waters. This environmental presence of
highly active chemicals may have unforeseeable eff ects on
the ecosystem.
Towards a Healthier EnvironmentCertified Reference Materials for Environmental Analysis of Pharmaceuticals
Matthias Nold, Product Manager Analytical Standards [email protected]
Cat. No. Brand Description Package Size
PHR1005 Fluka® Acetaminophen 1 g
PHR1127 Fluka Amoxicyllin trihydrate 1 g
PHR1067 Fluka Carbamazepine 1 g
PHR1412 Fluka Chloramphenicol 1 g
PHR1167 Fluka Ciprofloxacin 1 g
PHR1038 Fluka Clarithromycin 500 mg
PHR1058 Fluka Clotrimazole 1 g
PHR1144 Fluka Diclofenac sodium salt 1 g
PHR1145 Fluka Doxycycline hyclate 1 g
PHR1039 Fluka Erythromycin 1 g
PHR1246 Fluka Fenofibrate 500 mg
PHR1049 Fluka Gabapentin 1 g
PHR1004 Fluka Ibuprofen 1 g
PHR1247 Fluka Indomethacin 500 mg
PHR1084 Fluka Metformin hydrochloride 500 mg
PHR1076 Fluka Metoprolol tartrate 1 g
PHR1040 Fluka Naproxen 500 mg
PHR1308 Fluka Propranolol hydrochloride 1 g
PHR1389 Fluka Propyphenazone 1 g
PHR1126 Fluka Sulfamethoxazole 1 g
PHR1041 Fluka Tetracycline hydrochloride 500 mg
PHR1056 Fluka Trimethoprim 1 g
Table 1 Some Pharmaceuticals with Potential Relevance for Environmental Analysis and Proposed CRMs
9
sigma-aldrich.com/pharmastandards
Sta
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Inorganic Custom StandardsAn Interactive Online Platform
With a few simple mouse clicks, you can defi ne
your own multi-component standards for ICP and IC
in TraceCERT® quality, using our Inorganic Custom
Standards Online Platform:
sigma-aldrich.com/csp
For all TraceCERT Custom Standards we guarantee:
• Certification under double accreditation following
ISO/IEC 17025 and ISO Guide 34
• Highest level of accuracy and reliability
• Minimized uncertainties and lot-specific values
• Traceability to at least two independent references
(i.e., NIST, BAM or SI unit kg)
• Printed certificate according to ISO Guide 31
• Light and gas-tight aluminum foil bag packaging
allowing up to four years’ shelf life
Several aspects need to be considered for the priorisation
of pharmaceuticals for environmental monitoring: The
ecotoxicological potential, the occurence in the aquatic
environment and the annual consumption of the drug.
To ensure reliable and traceable quantitative results, ISO 17025
accredited labs should use proper certifi ed reference materi-
als (CRMs). For this purpose, Sigma-Aldrich® off ers a compre-
hensive portfolio of pharmaceutical compounds (APIs, related
substances and excipients) of pharmaceutical secondary
standards. Though these products have been developed for
use in pharmaceutical quality control and are traceable to
pharmacopoeia compendial standards, they are also certifi ed
reference materials by the defi nition of ISO, as they are manu-
factured under ISO/IEC17025 and ISO Guide 34 double
accreditation, and a certifi ed value, including uncertainty, is
given in addition to the pharmacopoeia traceable values. The
list on the previous page shows some common pharmaceuti-
cals and proposed certifi ed reference materials. The complete
portfolio comprises over 400 products and can be found at
sigma-aldrich.com/pharmastandards
To complement this offering, Sigma-Aldrich also offers a
comprehensive portfolio of pharmaceutical metabolites
and isotope labeled pharmaceuticals (sigma-aldrich.com/
pharmametabolites) as presented in an article in the pre-
vious issue of Analytix[5].
References
[1] www.basel.setac.eu/?contentid=763
[2] www.epa.gov/ppcp/
[3] Bergmann, A. et al. Zusammenstellung von Monitoringdaten
zu Umweltkonzentrationen von Arzneimitteln UBA-FB 001525;
2011.
[4] http://ec.europa.eu/environment/water/water-dangersub/
lib_pri_substances.htm#prop_2011_docs
[5] Richter, E. Analytix 3/2014, page 8
10
Pesticide StandardsFor Food & Environmental Analysis
• Neat Standards
• Single and Multi-Component Solutions
• Certified Reference Materials (CRMs)
• Matrix CRMs
• Isotopically Labeled Internal Standards
• Pesticide Metabolite Standards
• Proficiency Testing Materials (PT)
D Cl
Cl
D
DCl
Cl
D
D
Cl
ClDNH
S
N
O
CD3
DCD3
O
O N
N
Cl
N
NH
NO2
D D
D
D
Sta
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s
Short Overview of Sigma-Aldrich’s Isotope Labeled Pesticide StandardsInternal Standards for Food and Environmental Analysis
The Sigma-Aldrich® pesticide standards product line is the most compre-
hensive portfolio available on the market. We proudly off er more than
1300 high-purity pesticide and pesticide metabolite standards and certi-
fi ed reference materials for food and environmental analysis.
Our comprehensive portfolio includes several isotope-labeled pesticide
standards. To determine matrix eff ects and result bias due to a loss of the
analyte during the workup process, isotope-dilution mass spectrometry
is often applied. This technique takes advantage of the fact that isotope-
labeled compounds have nearly the same physical properties as the
non-labeled analogues, and thus the same behavior in the workup and
sample-preparation process. However, they can be distinguished in mass
spectrometry. Therefore, by spiking the sample before workup with an
isotope-labeled analogue, material loss during workup can be deter-
mined and compensated.
Please fi nd below a list of our current products. For more information,
please visit our Web page at sigma-aldrich.com/pesticides or order
our brand NEW brochure at sigma-aldrich.com/lit-request
Eva Katharina Richter, Product Manager Analytical Standards [email protected]
Cat. No. Brand Description Package Size
39246 Fluka® Acetamiprid-d3 50 mg
34086 Fluka Alachlor-d13 10 mg
32440 Fluka Amitraz Metabolite BTS 27271
(N/methyl-d3)
10 mg
34053 Fluka Atrazine-d5 10 mg
32965 Fluka Bentazon-d7 10 mg
34164 Fluka Bis(2-ethylhexyl)phthalate-3,4,5,6-d4 25 mg
32413 Fluka Carbendazim-d3 10 mg
34019 Fluka Carbofuran-d3 10 mg
32232 Fluka 6-Chloro-2,4-diamino-1,3,5-triazine-13C3 10 mg
56816 Fluka Clothianidin-d3 50 mg
34021 Fluka 4,4’-DDT-d8 10 mg
34169 Fluka Dibutyl phthalate-3,4,5,6-d4 25 mg
32381 Fluka NEW DEET-(diethyl-d10) 25 mg
48049 Supelco 1,4-Dichlorobenzene-d4 solution;
2000 μg/mL in methanol
1 mL
442247 Supelco 1,4-Dichlorobenzene-d4 1000 mg
442228 Supelco 1,2-Dichloroethane-d4 1000 mg
34233 Fluka Dicamba-d3 10 mg
34186 Fluka Dicyclohexyl phthalate-d4 10 mg, 25 mg
32311 Fluka NEW Diflubenzuron-(chlorophenyl-13C6) 10 mg
32274 Fluka NEW 4-(3,6-Dimethyl-3-heptyl)phenol-
3,5-d2 solution; 100 μg/mL in acetone
1 mL
34201 Fluka Dimethyl-d6 phthalate 25 mg
34018 Fluka Diuron-d6 10 mg
34214 Fluka DNC-d8 10 mg
03811 Fluka α-HCH-d6 5 mg
34170 Fluka Imidacloprid-d4 10 mg
34017 Fluka Isoproturon-d6 10 mg
32300 Fluka NEW Methiocarb-(N-methyl-d3) 10 mg
32668 Fluka Nabam-d4 10 mg
48715-U Supelco Naphthalene-d8 solution;
2000 μg/mL in methylene chloride
1 mL
33452 Fluka Parathion-ethyl-d10 10 mg
34209 Fluka Pirimicarb-d6 10 mg
34054 Fluka Simazine-d10 10 mg
43293 Fluka NEW Tebuconazole-(trimethyl-13C3) 5 mg
38176 Fluka Thiamethoxam-d3 25 mg
33853 Fluka Thionazin-d10 10 mg
34023 Fluka Trichloroanisole-d5 50 mg
Table 1 Neats and Solutions for Isotope-Labeled Pesticides
sigma-aldrich.com/pesticides
Figure 1 Molecular Structure of Deuterated α-HCH Figure 2 Molecular Structure of Deuterated Bentazon Figure 3 Molecular Structure of Deuterated
Imidacloprid
11
Organic TraceCERT® CRMs The Newest Product Additions to our Organic Neat Certified Reference Material Portfolio
Matthias Nold, Product Manager Analytical Standards [email protected]
For accredited testing labs, the availability of reliable and
traceable certifi ed reference materials (CRMs) is crucial since
the use of CRMs for calibration is demanded by ISO/IEC
17025. For the certification of Sigma-Aldrich®’s organic
TraceCERT products, high-performance quantitative NMR
(HP-qNMR®) is applied as a relative primary method to
achieve traceability to NIST SRM. If you would like to learn
more about qNMR and Sigma-Aldrich’s in-house capabili-
ties in this fi eld, please refer to the references cited below.
The organic TraceCERT reference materials are character-
ized by:
• Certified content by quantitative NMR (qNMR)
• Manufactured under ISO/IEC 17025 / ISO Guide 34
double accreditation
• Superior level of accuracy, calculated uncertainties, and
lot-specific values
• Traceability to NIST SRM
• Comprehensive documentation delivered with the
product (certification according to ISO Guide 31)
In the last issue of Analytix, we presented 25 new products,
and we are now able to present the latest additions to the
rapidly growing organic TraceCERT product line. You can
fi nd a list of the complete portfolio of over 150 products at
sigma-aldrich.com/organiccrm
Cat. No. Brand Product Package Size
63634 Fluka® Acetophenone 50 mg
14181 Fluka Dimethyl isophthalate 100 mg
97627 Fluka Monoethanolamine 100 mg
80026 Fluka 2,4,6-Tribromophenol 100 mg
67180 Fluka 1,2,4-Trichlorobenzene 100 mg
53766 Fluka 2,4,6-Trimethylphenol 100 mg
30304 Fluka Vanillin 50 mg
50409 Fluka Thymol 1 g
References
[1] Weber, M.; Hellriegel, C.; Rueck, A.; Sauermoser, R.; Wuethrich, J.
Using high-performance quantitative NMR (HP-qNMR®) for
certifying traceable and highly accurate purity values of
organic reference materials with uncertainties <0.1 %,
Accred. Qual. Assur. 18. 2013, 91– 98
[2] TraceCERT® Organic Certified Reference Materials, Analytix,
Vol. 3 2010; Vol. 1 2011; Vol. 3 2011; Vol. 4 2011.
[3] TraceCERT® Organic Certified Reference Materials, Analytix,
Vol. 2 2010.
Sta
nd
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s
sigma-aldrich.com/organiccrm
NEW FROM SIGMA-ALDRICH®
Certifi ed Reference Materials (CRMs)For the Petrochemical Industry
From ISO/IEC 17025 and ISO Guide 34 Accredited leading producer, Paragon Scientifi c
The Paragon range includes more than 600 products with a wide variety of Petrochemical
Certifi ed Reference Materials.
For more information, visit sigma-aldrich.com/paragon
12S
tan
da
rds
New clinical applications are emerging that monitor hormone levels for
the diagnosis and treatment of pain. Pain management clinics, for
example, are increasingly quantifying neurosteroids, corticosteroids,
and other hormones by LC-MS/MS and other analytical methods for
indication of abnormal hormone production and its relationship to
severe pain.[1,2] According to one study, serum levels of hormones such
as cortisol, pregnenolone, testosterone, thyroid, and dehydroepiandros-
terone (DHEA) represent the most objective biomarkers of severe,
uncontrolled pain.[1]
The study’s author stated that patients taking opioids for treatment of
pain should be screened for hormone abnormalities. Several hormones,
including cortisol, testosterone, and pregnenolone, are suppressed by
opioids with longer-acting opioids the most eff ective at hormone sup-
pression. Replacement hormone therapy may be needed to counteract
the eff ect of opioids on serum hormone levels. For pain patients with
abnormally low hormone levels that are not taking opioids, treatment
with neuroregenerative hormones such as hCG or human chorionic
gonadotropin may provide a benefi t of pain reduction.[1]
Testosterone and cortisol have also been implicated in neonatal[3] and
adult pain-related stressors.[4,5] In these studies, testosterone and cortisol
levels in blood, saliva, or hair were determined using immunoassay and
related analytical techniques. The fi ndings from these studies demon-
strate the importance and infl uence of cortisol and testosterone levels
on pain and pain thresholds during times of high stress.[3,4,5]
To view Cerilliant’s extensive catalog of solution Certified Reference
Materials (CRMs), including hormone categories such as corticosteroids,
DHEA, progestogens, testosterone, and thyroid, visit
sigma-aldrich.com/cerilliant
Register at sigma-aldrich.com/registercerilliant to receive news on
the latest reference standards being developed by Cerilliant.
New and Emerging Clinical Testing Applications: Monitoring Hormone Levels during Treatment of PainSolution CRMs for Corticosteroids, Progestogens and Other Hormones
Derrell Johnson, Manager, New Product Strategy & Tactical Marketing [email protected]
Maximilian Magana, Technical Marketing Specialist [email protected]
sigma-aldrich.com/cerilliant
Cerilliant Hormone Certified Spiking Solutions®
Cat. No. Description Package Size
Corticosteroids
A-096 Aldosterone 100 μg/mL in Acetonitrile
C-106 Cortisol 1.0 mg/mL in Methanol
C-113 Cortisol-D4 100 μg/mL in Methanol
C-117 Corticosterone 1.0 mg/mL in Methanol
C-130 Cortisone 100 μg/mL in Methanol
D-061 11-Deoxycortisol 1.0 mg/mL in Methanol
D-062 21-Deoxycortisol 100 μg/mL in Methanol
D-076 21-Deoxycortisol-D8 100 μg/mL in Methanol
D-078 11-Deoxycortisol-D5 100 μg/mL in Methanol
D-085 Dexamethasone 1.0 mg/mL in Methanol
D-105 11-Deoxycorticosterone 100 μg/mL in Methanol
Progestogens
H-085 17α-Hydroxyprogesterone 1.0 mg/mL in Methanol
H-096 17α-Hydroxyprogesterone-D8 100 μg/mL in Methanol
H-100 17α-Hydroxyprogesterone-2,3,4-13C3 100 μg/mL in Methanol
H-105 17α-Hydroxypregnenolone 100 μg/mL in Methanol
P-069 Progesterone 1.0 mg/mL in Acetonitrile
P-070 Progesterone-D9 100 μg/mL in Acetonitrile
P-104 Pregnenolone Coming Soon
Dehydroepiandrosterone (DHEA)
D-063 DHEA 1.0 mg/mL in Methanol
D-064 DHEA-D5 100 μg/mL in Methanol
D-065 DHEAS 1.0 mg/mL (as free sulfate) in
Methanol
D-066 DHEAS-D5 100 μg/mL (as free sulfate) in
Methanol
Testosterone
D-073 5α-Dihydrotestosterone (DHT) 1.0 mg/mL in Methanol
D-077 5α-Dihydrotestosterone-D3 100 μg/mL in Methanol
H-059 6β-Hydroxytestosterone 100 μg/mL in Methanol
T-034 6β-Hydroxytestosterone-D3 100 μg/mL in Methanol
T-037 Testosterone 1.0 mg/mL in Acetonitrile
T-046 Testosterone-D3 100 μg/mL in Acetonitrile
T-070 Testosterone-2,3,4-13C3 100 μg/mL in Acetonitrile
Thyroid
T-073 L-Thyroxine (T4) 100 μg/mL in 0.1N NH3 in Methanol
T-074 3,3',5-Triiodo-L-thyronine (T3) 100 μg/mL in 0.1N NH3 in Methanol
T-075 3,3',5'-Triiodo-L-thyronine (Reverse T3) 100 μg/mL in 0.1N NH3 in Methanol
T-076 L-Thyroxine-13C6 (T4-13C6) 100 μg/mL in 0.1N NH3 in Methanol
T-077 3,3',5-Triiodo-L-thyronine-13C6 (T3-13C6) 100 μg/mL in 0.1N NH3 in Methanol
T-078 3,3',5'-Triiodo-L-thyronine-13C6
(Reverse T3-13C6)
100 μg/mL in 0.1N NH3 in Methanol
References[1] Hughes, D. Hormone Levels Can Validate Presence of Pain and Affect Treatment.
Accessed 11 April 2014 from: www.empr.com/hormone-levels-can-validate-presence-of-pain-and-affect-treatment/article/310528/
[2] Tennant, F. The Use of Hormones in Chronic Pain.Accessed 11 April 2014 from: www.journalofprolotherapy.com/pdfs/issue_08/issue_08_06_hormones_for_pain.pdf
[3] Grunau, R. E.; Cepeda, I. L.; Chau C. M. Y.; Brummelte S.; Weinberg J.; Lavoie P. M.; Ladd M.; Hirschfeld A. F.; Russell E.; Koren G.; Van Uum S.; Brant R.; and Turvey S. E. Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age. Accessed 29 May 2014 from: www.ncbi.nlm.nih.gov/pmc/articles/PMC3774765/#__ffn_sectitle
[4] Choi J. C.; Chung M. I.; and Lee Y. D. Modulation of pain sensation by stress-related testosterone and cortisol. Accessed 29 May 2014 from: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.2012.07267.x/pdf
[5] Karlén J.; Ludvigsson J.; Frostell A.; Theodorsson E.; and Faresjö, T. Cortisol in hair measured in young adults – a biomarker of major life stressors? Accessed 29 May 2014 from: www.biomedcentral.com/1472-6890/11/12#B37
13
sigma-aldrich.com/derivatization
Sta
nd
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s
New! Brochure for Cosmetic Standards For Beauty with Safety
For precise quality control of raw materials or formulated personal-care and cosmetic products,
we off er analytical standards for several groups of ingredients, including:
• Antibacterial, antifungal substances
• Colorants
• Emulsifiers, thickeners, opacifiers
• Fragrances
• Metals
• PAHs
• Plasticizers
• Preservatives
• Propellants
• UV blockers
Order the brand NEW brochure or visit sigma-aldrich.com/cosmetics for an up-to-date product list.
New TLC Staining Solution for Boronic Acids Curcumin solution 28982 eff ectively stains various types of boron containing species,
such as:
• Free boronic acids
• Boronic acid pinacol esters
• Potassium trifluoroborate salts
For rapid monitoring of your Suzuki-Miyaura cross-coupling, or any other organic reaction
involving boronic acids and related derivatives, try curcumin solution 28982.
For more information on TLC derivatization, visit sigma-aldrich.com/derivatization
Reference:
[1] Lawrence, K.; Flower, S. E.; Kociok-Kohn, G.; Frost, C. G.; James, T. D. A simple and effective
colorimetric technique for the detection of boronic acids and their derivatives. Anal. Methods
2012, 4, 2215–2217.
1 691615 (+)-Vinylboronic acid pinanediol ester;
2 674710 3-Methoxy-1-propyn-1-ylboronic acid
pinacol ester;
3 346225 (2-Methylpropyl)-boronic acid;
4 683590 Potassium trans-3-methoxy-1-
propenyltri-fluoroborate
14
sigma-aldrich.com/lc-ms
Introduction
In routine LC-MS analysis, reliability of methods is crucial in
order to avoid false analytical data or increase in time per
sample due to necessary corrections or repetition of deter-
minations. Besides instrument sensitivity, which generally
improves with every generation, solvent quality plays an
increasingly important role. Lesser-grade solvents may con-
tain impurities, and are not tested for LC-MS applications,
resulting in interferences or signal suppression. Impurities
that most commonly cause problems are high alkali-ion
concentrations, plasticizers and detergents.
Experimental
A mixture containing 6 alkylresorcinols (phenolic lipids
used as food intake biomarkers) at 0.1 μg/mL was separated
on a Titan C18 UHPLC column, using a previously published
method (Ross 2012). [1]
The following conditions were employed, with determina-
tions using fi rst LC-MS CHROMASOLV® methanol, then stan-
dard HPLC grade methanol, before switching back to LC-MS
methanol. The standard mixtures were created in neat
methanol.
Column Supelco Titan™ C18 1.9 μm 2.1x100 mm
Mobile phase A = mQ water, B = MeOH (LC-MS
CHROMASOLV or standard HPLC grade)
Gradient min %B
0 89
6 99
7 99
8 89
10 89
Flow 0.65 mL/min
Injection volume 1 μL
MS APCI+ operated in MRM mode
Instrument Shimadzu LCMS-8030plus including Nexera
LC-30AD pumps, Nexera SIL-30AC autosampler,
Nexera CTO-20AC column oven, Prominence
DGU-20A 5r degasser and Shimadzu 8030plus
triple quadrupole
Choosing the Right Solvent for Your Application…and Avoiding Signal Suppression in MS
Matthias Drexler, Product Manager, Analytical Reagents and Spectroscopy [email protected]
Experimental data courtesy of Otto Savolainen and Alastair Ross at Chalmers University of Technology, Gothenburg, Sweden
Results
Figure 1 clearly shows all key analytes are separated, ionized
and detected with the selected method when utilizing a
gradient of mQ water and LC-MS CHROMASOLV methanol.
The instrument was then run with two blanks containing
standard HPLC grade methanol, after which the same ana-
lyte mixture was analyzed again. Immediately strong signal
suppression can be seen in the resulting chromatogram
(see Figure 2). The eff ect is especially apparent for the ana-
lytes with longer retention time. After 10 injections working
with HPLC grade methanol, the suppression effects are
even higher (Figure 3) leading to complete suppression of
some of the analyte signals after a few dozen injections.
The instrument becomes “blind” to the analytes at these
concentrations.
After switching back to a gradient containing LC-MS grade
methanol, two blanks were run before injection of the analyte
mix and running the method again. In Figure 4, only minimal
(if at all) remaining signal suppression can be seen and all
6 analytes can again be clearly detected and quantifi ed.
Conclusion
These results show the importance of choosing the right
solvent quality to support the analytical task at hand. High
purity and sensitive UV gradient methods can give only a
rough picture of a solvent and its suitability for MS detec-
tion. Relying on sub-par solvents, especially during method
development, may lower the apparent cost per sample, but
have a serious negative impact on limit of quantification
(LOQ), while also negatively affecting the lifetime of the
instrument.
Our LC-MS CHROMASOLV solvents are application tested,
off er low cation impurities, and high reliability to help sci-
entists to avoid the hidden costs resulting from signal sup-
pression. More information can be found at
sigma-aldrich.com/lc-ms
Ch
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15
sigma-aldrich.com/uhplc
Cat. No. Featured and Related Products Package Size
Solvents
34967 Acetonitrile, LC-MS CHROMASOLV 250 mL, 1 L, 2.5 L, 4x4 L, 6x1 L, 4x2.5 L, 20 L
34966 Methanol, LC-MS CHROMASOLV 1 L, 2.5 L, 4x4 L, 6x1 L, 4x2.5 L
39253 Water, LC-MS CHROMASOLV 1 L, 4x4 L, 20 L
14261 Acetonitrile, LC-MS Ultra CHROMASOLV, for UHPLC-MS 1 L, 2 L
14262 Methanol, LC-MS Ultra CHROMASOLV, for UHPLC-MS 1 L, 2 L
14263 Water, LC-MS Ultra CHROMASOLV, for UHPLC-MS 1 L, 2 L
Columns and Accessories
577124-U Titan C18 UHPLC Column, 1.9 micron, 10 cm x 2.1 mm 1 ea
577127-U Titan C18 UHPLC Guard Cartridge, 1.9 micrometer, 1.9 μm particle size, L × I.D. 5 mm × 2.1 mm 3 ea
577133-U Titan C18 UHPLC Guard Cartridge Holder, 1.9 micron, for use with Titan Guard Cartridges 1 ea
Analytical Standards of Alkylresorcinols
56453 5-Tridecylresorcinol 10 mg
91822 5-Pentadecylresorcinol 10 mg
97001 5-Heptadecylresorcinol 10 mg
49519 5-(Nonadecyl-1,1,2,2-d4)resorcinol 10 mg
57981 5-Nonadecylresorcinol 10 mg
53503 5-Eicosylresorcinol 10 mg
50851 5-Heneicosylresorcinol 10 mg
03422 5-Tricosylresorcinol 10 mg
0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 5,5 6,0 6,5 7,0 7,5 8,0 8,5 9,0 9,5 min
0,0
0,5
1,0
1,5
2,0
2,5
3,0
3,5
4,0
(x1,000)
0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 5,5 6,0 6,5 7,0 7,5 8,0 8,5 9,0 9,5 min
0,00
0,25
0,50
0,75
1,00
1,25
1,50
1,75
2,00
2,25
2,50
2,75
3,00
3,25
3,50
3,75
4,00
(x1,000)
0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 5,5 6,0 6,5 7,0 7,5 8,0 8,5 9,0 9,5 min
0,00
0,25
0,50
0,75
1,00
1,25
1,50
1,75
2,00
2,25
2,50
2,75
3,00
3,25
3,50
(x1,000)
0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 4,5 5,0 5,5 6,0 6,5 7,0 7,5 8,0 8,5 9,0 9,5 min
0,00
0,25
0,50
0,75
1,00
1,25
1,50
1,75
2,00
2,25
2,50
2,75
3,00
3,25
3,50
3,75
4,00
(x1,000)
Figure 1 Chromatogram Using LC-MS CHROMASOLV Methanol in the Gradient Figure 2 Chromatogram after 2 Blanks Run and First Injection using Standard
HPLC Grade Methanol
Figure 4 Chromatogram after Switching back to a Gradient with LC-MS
CHROMASOLV Methanol and Running Two Blanks
Figure 3 Chromatogram after 10 Injections using a Gradient Containing Standard
HPLC Grade Methanol
For very sensitive UHPLC-MS instruments, we recommend using LC-MS
Ultra solvents, which are tested on UHPLC-(qTOF)MS both in positive
and negative mode, are fi lled in leach-resistant clear borosilicate bottles
for very low cation concentrations, and exhibit an extremely strong lot-
to-lot consistency to get the most out of today’s sensitive UHPLC-MS
instruments.
To learn more about LC-MS Ultra, visit sigma-aldrich.com/uhplc
References:
[1] Ross, AB. Analysis of alkylresorcinols in cereal grains and products using
ultra high-pressure liquid chromatography with fluorescence, ultraviolet,
and CoulArray electrochemical detection. Journal of Agricultural and Food
Chemistry 60, 2012, 8954 – 8962.
Ch
rom
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16C
hro
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sigma-aldrich.com/analytix
GC-Headspace SolventsSpecifically developed and optimized for sensitive static
GC-Headspace analysis of volatile organics.● High purity – microfiltered (0.2 μm)● Improved analyte recoveries● Longer shelf life – ed under inert gas● Specifications matching USP, Ph.Eur. & ICH guidelines
For additional information, visit us at sigma-aldrich.com/gc-hs.
Description Size Cat. No.
1,3-Dimethyl-2-imidizolidinone 1 L 67484
N,N-Dimethylacetamide 1 L 44901
Dimethyl sulfoxide 1 L 51779
N,N-Dimethylformamide 1 L 51781
Water 1 L 53463
1-Methyl-2-pyrrolidinone, for GC-HS 1 L 69337
Benzyl alcohol 1 L 80708
LC-MS Ultra Solvents and Additives Designed for UHPLC Quality exceeding your expectations
Purity for low detection limits
• Suitability tested by UHPLC-MS/TOF
• Lot-to-lot reproducibility
• Microfiltered (0.1 μm), filled in clear borosilicate glass containers
For more information or to request a LC-MS Ultra CHROMASOLV Solvents
and Additives Brochure (OUX), please visit sigma-aldrich.com/uhplc
17
Se
nso
rics
A Remarkable Carbonate-Selective Ionophore for the Determination of Oceanic Carbon Dioxide Using an Ion-Selective Electrode
Potentiometric detectors based on ion-selective electrodes
are used in a wide range of applications for detecting vari-
ous ions important in the clinical, environmental and indus-
trial areas because they offer advantages such as high
selectivity, sensitivity, good precision, simplicity, portability,
non-destructive analysis, and low cost[1].
To map out the global carbon cycle, it is very important to
know detailed information about the spatial and temporal
variations in inorganic carbons in oceans, especially in rela-
tion to the air-sea redistribution of the rapidly increasing
anthropogenic carbon dioxide in the atmosphere and its
infl uence on the greenhouse eff ect[2].
A frequently measured parameter to quantify the oceanic
carbon system is the total CO2 in seawater. It is estimated
from the total alkalinity determined by potentiometric
titration or from the concentration of dissolved CO2 mea-
sured directly with coulometric methods, infrared spectros-
copy, and gas chromatography, which, in seawater, is not
trivial and often requires rather elaborate instrumentation.
Under normal seawater conditions, CO2(aq) is a minor species
(<1%), and the concentration of CO32- is about 10 –11% of the
total inorganic carbons. Hence, considering the relative
abundance of CO32- ion in seawater, carbonate-selective
electrodes should be used in seawater analysis.
Nam et al. synthesized a new carbonate-selective iono-
phore (93206) that behaves like a molecular tweezer; two
trifl uoroacetophenone groups were attached to a rigid cho-
lic acid derivative (Figure 1). The observed carbonate selec-
tivity of log K PotCO3,Cl
= -6.8 of the electrode over chloride and
other anions (incl. lipophilic ones) appeared to be high
enough to apply to seawater analysis.
Daniel Weibel, Product Manager Analytical Reagents [email protected]
Using 93206 as ionophore in the electrode, the total CO2
level was measured in Yellow Sea water, providing a fast,
stable, and reproducible potentiometric response. In this
manner, the level of total CO2 was determined to be
1.94 ± 0.03 (n = 15) mmol/kg seawater, which was found to
be in good agreement to values determined by a CO2 gas
sensor and a standard potentiometric titration method.
Recommended Membrane Composition (% by wt.)
Cat. No. Description wt%
93206 Carbonate ionophore VII 5.1%
91661 Methyltridodecylammonium chloride 1.2%
02138 Bis(1-ethylhexyl)adipate 56.8%
81392 Poly(vinyl chloride) 36.9%
Dissolved in ethyl acetate and THF (3:5 v/v)
Recommended Cell Assembly
Reference || sample solution || liquid membrane |
0.1 M NaH2PO4, 0.1 M Na2HPO4, 0.01 M NaC | AgCl, Ag
Electrode Characteristics and Function
Selectivity Coef ficients log K PotNa,M
as obtained by the
matched potential method at pH 8.0 (0.1 M Tris-H2SO4):
log K PotCO3,Cl : -6.8 log K Pot
CO3,NO3 : -4.5 log K PotCO3,Salicylate : -1.3
log K PotCO3,Br
: -6.7 log K PotCO3,NO2
: -4.8
log K PotCO3,ClO : -2.0 log K
PotCO3,SCN : -2.8
Slope: -26.0 mV/dec
Detection level: 5.8*10-7 mol/L CO32-
For more information on our sensoric applications, visit
sigma-aldrich.com/selectophore
OCH3
O
N(C8H17)2
H3C
CH3
O
O
O
O
H
H
H H
H
F3COC
CH3
O
O
N(C8H17)2CH3
CH3
O
O
COCF3
COCF3
F3COC
References:
[1] Selectophore® Ion Sensor Materials; Sigma-Aldrich Co.: St. Louis, MO, 2011.
[2] Choi, Y. S.; Lvova, L.; Shin, J. H.; Oh, S. H.; Lee, C. S.; Kim, B. H.; Cha, G. S.; Nam, H. Determination of Oceanic Carbon Dioxide Using a
Carbonate-Selective Electrode. Anal. Chem. 2002, 74, 2435 –2440.
sigma-aldrich.com/selectophore
Figure 1 Structural Representations of the Carbonate-Selective Ionophore 93206, Indicating the Tweezer-Like Shape of the Molecule on the Right.
18
sigma-aldrich.com/ipc
Spec
trom
etry
In previous publications, di- and tri-cationic ion-pair reagents were used to detect inorganic compounds, such as chlorides and sulfates.[1-2]. A recent publication by C. Xu et al [3] demonstrates the versatility of such ion-pair reagents, which are added post-column to the mobile phase and increase the ESI-MS sensitivity extraordinarily by forming positively charged adducts of reagent and anionic analytes (Figure 1).
Figure 1 The Instrumental Setup of HPLC-PIESI-MS.
Since the aim of water analysis is the detection of the small-est amounts of pesticides in water or other biological matri-ces to understand the effect on health and the environ-ment, this new method supports analytical laboratories in this challenge.
LC-MS MethodThe different pesticides are separated on a Supelco Ascentis Express C18 (15 cm x 2.1 mm i.d., 2.7 µm particle size) column using a gradient from 95% 5 mmol/L formic acid/water and 5% 5 mmol/L formic acid/methanol to 5% aqueous buffer within 20 min at 0.4 mL/min. The ion-pair reagent is mixed to the LC flow post-column via a mixing tee with a flow rate of 0.1 mL/min. Injection volume of water samples is 25 µL (fixed loop). This method demonstrates a very good sensi-tivity with a standard LC-MS system. Table 1 shows the list of analytes analyzed with this technique.
A New Approach for the Detection of Acidic Pesticides in Water by MSIncreasing the Sensitivity in Pesticide Analysis by Paired-Ion ESI Detection
Jens Boertz, Product Manager Analytical Reagents [email protected] Köhling, Sr. Scientist [email protected]
Chengdong Xu, Graduate Student1, Zachary S. Breitbach, Research Scientist1, Daniel W. Armstrong, R.A. Welch Professor, 1Department of
Chemistry & Biochemistry, University of Texas at Arlington [email protected]
In Table 1 also the results for 19 acidic pesticides using three different ion-pairing reagents are presented. The lim-its of detection (LOD) of 19 pesticides obtained were in the range from 0.6 to 19 pg. The fourth ion-pairing reagent applied (1,9-Nonanediyl-bis(3-methylimidazolium) difluo-ride) did not show any improvement in terms of LOD. In total, this approach shows an increased sensitivity of one to three orders of magnitude for the pesticides analyzed.
A novel method based on paired-ion electrospray ioniza-tion (PIESI) mass spectrometry has been developed for determination of acidic pesticides at ultratrace levels in surface and ground waters. The proposed approach pro-vides greatly enhanced sensitivity for acidic pesticides and overcomes the drawbacks of the less sensitive negative ion mode ESI-MS. The limits of detection (LODs) of 19 acidic pesticides were evaluated with four types of dicationic ion-pairing reagents (IPR) in both single-ion monitoring (SIM) and selected-reaction monitoring (SRM) mode. The LOD of 19 pesticides obtained with the use of the optimal dica-tionic ion-pairing reagent ranged from 0.6 pg to 19 pg, indicating the superior sensitivity provided by this method. The transition pathways for different pesticide-IPR com-plexes during the collision-induced dissociation (CID) were identified. To evaluate and eliminate any matrix effects and further decrease the detection limits, off-line solid-phase extraction (SPE) was performed for DI water and a river water matrix spiked with 2000 ng/L and 20 ng/L pesticide standards respectively, which showed an average percent recovery of 93%. The chromatographic separation of the acidic pesticides was conducted by high-performance liquid chromatography (HPLC) using a C18 column (15 cm x 2.1 mm i.d., 2.7 µm particle size) in the reversed- phase mode using linear gradient elution. The optimized HPLC–PIESI-MS/MS method was utilized for determination of acidic pesticides at ng/L level in stream/pond water samples. This experimental approach is one to three orders of magnitude more sensitive for these analytes than other reported methods performed in the negative-ion mode.
[Dicat I]2+
MS pump water/
methanol
ESI-MS
Sample Solution
Supe
lco
Asc
entis
® Ex
pres
s C18
col
umn
LC pump 40 µM paired ion reagent
in water Mixing tee
[Analyte + Dicat I]+
Analyte™
19
sigma-aldrich.com/ipc
Sp
ect
rom
etr
y
Sample 1,5-Pentanediyl-bis(1-butylpyrrolidinium)
difluoride
1,3-Propanediyl-bis(tripropylphosphonium)
difluoride
1,5-Pentanediyl-bis(3-benzylimidazolium)
difluoride
SIM SRM SIM SRM SIM SRM
LOD (pg) m/za LOD (pg) m/zb LOD (pg) m/za LOD (pg) m/zb LOD (pg) m/za LOD (pg) m/zb
2,4-D 45 543.3 7.0 416.2 10 581.3 8.0 187.2 16 605.2 8.0 385.3
MCPA 3.6 523.4 1.1 396.3 15 561.3 15 187.2 10 585.3 10 385.3
2,4,5-T 25 577.3 3.7 450.2 16 615.3 24 187.2 25 639.2 3.7 385.3
2,4-DB 37 571.4 6.7 444.3 700 609.3 700 187.2 2000 633.3 2000 385.3
MCPB 30 551.4 9.0 424.3 1100 589.4 720 187.2 1300 613.3 1200 385.3
2,4,5-TB 32 605.3 6.0 478.3 1800 643.3 6000 187.2 5300 667.2 2500 385.3
Cloprop 9.0 523.4 2.7 396.3 10 561.3 10 187.2 7.0 585.3 3.5 385.3
Dichlorprop 30 557.3 4.5 430.3 20 595.3 12 187.2 10 619.2 4.0 385.3
Fenoprop 20 591.3 4.0 464.3 20 629.3 20 187.2 30 653.2 10 385.3
Mecoprop 30 537.4 12 410.3 3.8 575.4 2.8 187.2 15 599.3 4.7 385.3
Dicamba 15 543.3 3.0 416.3 6.5 581.3 6.5 187.2 6.0 605.2 2.6 385.3
2,3,6-TBA 110 547.3 6.3 420.2 60 585.2 60 187.2 17 609.2 3.8 385.3
Clopyralid 20 514.3 1.5 387.2 4.5 552.3 4.5 187.2 5.0 576.2 5.0 385.3
Quinclorac 6.0 564.3 0.60 437.2 7.5 602.3 7.5 187.2 10 626.2 3.0 385.3
Quinmerac 15 544.4 2.8 417.3 7.0 582.3 5.2 187.2 3.5 606.3 3.5 385.3
Flupropanate 5.0 469.4 5.0 342.2 3.5 507.3 1.1 187.2 3.1 531.3 0.088 385.3
MCA 6.0 417.3 3.0 290.2 10 455.3 35 187.2 17 479.2 15 385.3
TCA 160 485.2 19 359.3 1.5 523.2 2.0 187.2 15 547.1 7.5 385.3
Dalapon 10 465.3 0.75 359.3 5.0 503.3 5.0 187.2 15 527.2 2.9 385.3
Table 1 Limits of Detection of Pesticide Standard Solutions Obtained by PIESI-MS in the SIM Mode and SRM Mode with the Use of Dicationic Ion-Pairing Reagent.
a Indicates the mass-to-charge ratio of the complex monitored in the SIM mode.
b Indicates the mass-to-charge-ratio of the SRM fragment monitored in the SRM mode.
Cat. No. Name (Abbreviation) Exact Mass Package Size
31518 2,4-dichlorophenoxyacetic acid (2,4-D) 219.97 250 mg
45555 4-chloro-o-tolyloxyacetic acid (MCPA) 200.02 250 mg
45667 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) 253.93 250 mg
45420 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB) 248.00 250 mg
36145 4-(4-chloro-o-tolyloxy)butyric acid (MCPB) 228.06 100 mg
S412325 4-(2,4,5-trichlorophenoxy)butyric acid (2,4,5-TB) 281.96 25 mg
233013 2-(3-chlorophenoxy)propionic acid (cloprop) 200.02 50 g
45436 2-(2,4-dichlorophenoxy)propionic acid (dichlorprop) 233.99 250 mg
45691 2-(2,4,5-trichlorophenoxy)propionic acid (fenoprop) 267.95 250 mg
36147 2-(4-chloro-o-tolyloxy)propionic acid (mecoprop) 214.04 100 mg
45430 3,6-dichloro-2-methoxy-benzoic acid (dicamba) 219.97 250 mg
R169676 2,3,6-trichlorobenzoic acid (2,3,6-TBA) 223.92 25 mg
36758 3,6-dichloro-2-pyridine-carboxylic acid (Clopyralid) 190.95 250 mg
36521 3,7-dichloro-8-quinoline-carboxylic acid (Quinclorac) 240.97 250 mg
36522 7-chloro-3-methyl-8-quinoline-carboxylic acid (Quinmerac) 221.02 250 mg
402923 2-chloroacetic acid (MCA) 93.98 100 g
T6399 2,2,2-trichloroacetic acid (TCA) 161.90 5 g
35562 2,2-Dichloropropionic acid (dalapon) 141.96 250 mg
56618 1,5-Pentanediyl-bis(1-butylpyrrolidinium) difluoride solution 100 mL
75128 1,9-Nonanediyl-bis(3-methylimidazolium) difluoride solution 100 mL
42341 1,3-Propanediyl-bis(tripropylphosphonium) difluoride solution 100 mL
76507 1,5-Pentanediyl-bis(3-benzylimidazolium) difluoride solution 100 mL
53802 Supelco Ascentis Express ™ C18 (15 cm x 2.1 mm i.d.,
2.7 μm particle size)
1 EA
94318 Formic acid 50 mL, 250 mL
34485 Methanol 2.5 L, 4x2.5 L
Table 2 Chemicals Used to Carry Out HPLC-PIESI-MS Experiments .
References
[1] Köhling, R.; Reichlin, N.; Wille, G. Analytix No. 9.
[2] Köhling, R.; Reichlin, N.
Analytix No. 3.
[3] Chengdong X.; Armstrong, D. W.
Analytica Chimica Acta, 792. 2013 1–9.
20
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Do You Use IC High-Purity Certifi ed Reference Standards?In that case, check out our IC TraceCERT®!
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Water Determination in Pharmaceutical CompoundsKarl Fischer Titration with HYDRANAL® Reagents
Water-content determination is mandatory for many mate-
rials used in the manufacturing of medicines. Karl Fischer
(KF) titration is the long-standing standard method for this
analysis prescribed by the leading pharmacopoeias, such as
the European (Ph.Eur.), the United States (USP) and the Japa-
nese (JP).
Volumetric Karl Fischer Technique
The volumetric KF technique can be used for samples with
high water content (approx. 0.1–100%). The sample is added
to the titration vessel containing a suitable working medium,
such as Hydranal Methanol dry or Hydranal Solvent. With
the corresponding iodine-containing titrating agent,
Hydranal Composite or Hydranal Titrant, the water content
of the sample is determined by titration. End-point deter-
mination is carried out by applying a constant current and
measuring the voltage via double platinum electrode; or
vice versa, applying a constant voltage and measuring the
current. The water content is calculated from sample
weight, consumption of titrating agent, and water equiva-
lent (titer) of the titrating agent. Pharmaceutical com-
pounds such as ethosuximide, used for epilepsy treatment,
(application L510), or the cytostatic drug cyclophospha-
mide (application L463), can be analyzed according to stan-
dard procedures without interference. These titrations can
also be carried out in less toxic ethanol-based reagents, the
Hydranal E-types.
Coulometric Karl Fischer Technique
Samples with lower water content (up to 1%) can be ana-
lyzed using the coulometric KF method. The required
iodine is generated electrochemically in the titration vessel
by anodic oxidation of iodide, which is contained in the
Hydranal Coulomat reagents. The water content is calcu-
lated from the amount of the produced (consumed) elec-
tric current (which equals iodine consumption) over time.
Karl Fischer Oven Technique
Insoluble samples, samples that undergo side reactions
with the KF reagents, or samples that release their water
only at high temperatures, may be analyzed using the KF
oven. The water of the sample is driven out at a variable
temperature and transferred by a suitable carrier gas into
the KF titration vessel. The water content is determined
Andrea Felgner, Market Segment Manager [email protected]
according to standard procedures. 5-Aminolevulinic acid-
HCl (lyophilisate) shows a strong side reaction in methanol;
an end point cannot be reached with direct KF titration
methods. For this compound, we recommend determina-
tion with the KF oven in combination with the coulometric
titration technique, due to the low water content of this
substance. Suitable application parameters are (application
L506):
• Evaporation temperature 80 °C (decomposition of the
sample starts at 120 °C)
• Determination time 600 seconds
• Anolyte Hydranal Coulomat AG or Hydranal Coulomat
AG-Oven
• Catholyte Hydranal Coulomat CG
Side Reactions and pH-Influencing Samples
Substances containing nitrogen compounds may cause
interference with the pH value of the working medium.
Side reactions occur during the KF titration, possibly lead-
ing to coated electrodes, fading end points or no end
points at all, and erroneous results. These side reactions can
be suppressed through the addition of suitable buff er sub-
stances to the working medium in the titration vessel.
Benserazide hydrochloride, an active ingredient used in the
treatment of Parkinson’s disease, is an example of a nitro-
gen-containing substance. For correct determination of its
water content, Hydranal Buff er Base or a mixture of Hydranal
Methanol dry and salicylic acid should be used as a working
medium, and then be titrated with Hydranal Composite 2
(application L416). Profl avine hemisulfate, a topical antisep-
tic, also increases the pH value of the working medium and
no end point is achieved. Hydranal Buff er Base or a mixture
of Hydranal Methanol dry and benzoic acid can be used to
lower the pH value and prevent the side reaction; titrate
with Hydranal Composite 5 (application L354). Water-con-
tent determination in penicillin can also be disturbed by pH
infl uences; a side reaction occurs: penicillin derivatives such
as penicilloic acid and other hydrolysis products are oxi-
dized by iodine. By conducting the titration in weakly acidic
conditions, this side reaction can be suppressed. The KF
one-component technique with Hydranal Methanol dry or
Hydranal Methanol Rapid and Hydranal Composite 2 gives
a pH value of approximately 5 in the titration vessel. This is
Tit
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(continued on page 22)
22
sigma-aldrich.com/hydranal
suffi cient for titrating the water content in penicillin with-
out any side reactions. If an end point is not easily reached,
addition of salicylic acid to the working medium (before
pre-titration) is recommended. Titration of penicillin with
the KF two-component technique is also possible. A mix-
ture of Hydranal Solvent and salicylic acid is recommended
as a working medium and can be titrated with Hydranal
Titrant (application L166).
Enhancement of Sample Solubility
For samples that are only poorly soluble in the KF working
medium, Hydranal-Buffer Base or a mixture of Hydranal
Methanol dry and salicylic acid can be recommended as
working media to enhance solubility and therefore yield
correct determination results (titrating agent Hydranal
Composite). Examples are the beta-lactam antibiotics
amoxycillin-3-hydrate (application L352) or ampicillin
(application L422).
However, other substances such as riboflavin phosphate
sodium (biochemical cofactor, also used as a food dye)
prove insoluble in the alcohol-based KF media. As a suit-
able solubilizer for this compound, formamide is recom-
mended. It can be added to the working medium (volu-
metric KF technique) in a ratio of 1:1 (application L509).
Application Reports
All application reports can be obtained by contacting our
Hydranal technical service team ([email protected]). Visit
our Web site sigma-aldrich.com/hydranal for complete
product listings and more information on KF titration.
On our Web site sigma-aldrich.com/hydranal you will
fi nd more information about the Ph. Eur. requirements for
KF titration. Our Hydranal technical service team has carried
out suitability tests for a range of substances, which are
available upon request.
Take advantage of both our expertise gained from over
thirty years of experience and our extensive applications
database on KF titration. For any questions, help, or feed-
back, please visit our Web site or contact us (details below).
Figure 1 Application Report for Polysorbate 80 (L608)
Tit
rati
on
Cat. No. Description
L166 Penicillin-G sodium and penicillin-G-potassium
L230 Dobutamine hydrochloride
L242 Erythromycin
L249 Adenosine-5’-triphosphoric acid disodium salt
L297 Glycerine monostearate
L307 Benzyl penicillin procaine
L326 Magnesium stearate
L352 Amoxycillin-3-hydrate
L354 Proflavine hemisulfate
L416 Benserazide hydrochloride
L422 Ampicillin
L448 Gentamicin sulfate
L463 Cyclophosphamide
L489 Disodium hydrogen phosphate-12-hydrate
L506 Aminolevulinic acid-HCl (Lyophylisate)
L509 Riboflavin phosphate sodium
L510 Ethosuximide
L604 Povidon
L607 Sorbitol solution (70%)
L608 Polysorbate 80
L660 Ibuprofen (film tablets)
L661 Zineb
L664 Niclosamide hydrate
L670 Atrazine desisopropyl
L675 Atrazine desisopropyl-2-hydroxy
L698 Asulam
Table 1 Selected Application Reports for the Pharmaceutical
Industry
23
sigma-aldrich.com/hydranal
Cat. No. Description
Reagents for Volumetric KF Titration
34805 Hydranal Composite 5, reagent for one-component KF titration
34806 Hydranal Composite 2, reagent for one-component KF titration
37817 Hydranal Methanol Rapid, working medium for fast one-component KF titration
34741 Hydranal Methanol dry, working medium for one-component KF titration
34801 Hydranal Titrant 5, reagent for two-component KF titration
34811 Hydranal Titrant 2, reagent for two-component KF titration
34800 Hydranal Solvent, working medium for two-component KF titration
34724 Hydranal Formamide dry, solvent for KF titration
34804 Hydranal Buffer Acid, buffer substance for KF titration
37859 Hydranal Buffer Base, buffer substance for KF titration
37865 Hydranal Salicylic Acid, buffer substance for KF titration
32035 Hydranal Benzoic Acid, buffer substance for KF titration
Reagents for Coulometric KF Titration
34836 Hydranal Coulomat AG, anolyte reagent
34739 Hydranal Coulomat AG-Oven, anolyte reagent for KF oven
34840 Hydranal Coulomat CG, catholyte reagent for cells with diaphragm
Water Standards for KF Titration
34849 Hydranal Water Standard 10.0, 1 g contains 10.0 mg = 1.0% water, tested against NIST SRM 2890 (exact value on CoA)
34828 Hydranal Water Standard 1.0, 1 g contains 1.0 mg = 0.1% water, tested against NIST SRM 2890 (exact value on CoA
34847 Hydranal Water Standard 0.1, 1 g contains 0.1 mg = 0.01% water, tested against NIST SRM 2890 (exact value on CoA)
34696 Hydranal Standard sodium tartrate dihydrate, solid standard for volumetric KF titration, water content ~15.6% (exact value on CoA)
Table 2 Selected Hydranal Reagents for KF titration
Request the new Hydranal Product Line Overview brochure
• Volumetric Titration with One-Component Reagents
• Volumetric Titration with Two-Component Reagents
• Coulometric Titration with Hydranal Coulomat
• Hydranal Water Standards
• Hydranal E-Type Reagents
• Reagents for Ketones and Aldehydes
• Technical Support
Order this brochure by returning the attached business reply card or visit
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