~jaj' vi .~4 .:>.,ij1 ':>:;:;~) 'p yl; 0' j~ -...

.,.~

..~-'"

J. Saudi Chern. Soc., Vol. 12, No. I; pp. 35-46 (2008) 35

SPECTROPHOTOMETRIC DETERMINATION OF NAFCILLIN SODIUM IN PURE FORM,TABLETS AND BIOLOGICAL FlUIDS

Nawal A.AI-Arfaj*, Sawsan A.Abdel-Razeq and Aziza A. AI-HoshanChemistry Department, College of Science, Wo~en Student Medical Studies and Sciences Sections,

King Saud UniversityP.O.Box 22452, Riyadh 11495, Saudi Arabia.

:. (Received 31 Sl Dec. 2007; Accepted 25th Feb. 2008)

4,,11 ).AJI "",I }~, J) ~\ .; J","" J i J'-.).,..,.)\ ~l; ..,.oS' .". flJ:.;J 4...~\) :i\1.-,J' :o.:A:1.I' J JaJ' .:.r- ':':;:;\ ..; ) f

J..;.15' .)-"'"~ J J~' o1i.JJ..' J! 1oS'~' o1i.JJ..I .=.-l;J'-1 J\;>' Js- .I ;aj J)~' ~JaJI .~?I ~, y'-,,"" J)

.:.r- 4:llSo ~J.) Js- JlA."pJl ~, .:>.,iJ1 ).) .:Jt)~1 ~ .:>~ ~ iJ'-.).,..,.)1 ~l; ~'y .:;));;L:.;;J)~'

j&ow Js- .L..;..:j ~W\ ~JaJ' vi .~4 .:>.,iJ1 ':>":;:;~) 'p yl; 0' - I.i"" y J~ ~ ~-l$jJ,) .=.-~,

':>.,Lo ~ .:> ~ ~ .=.-l; ).?J")IJ j;A;-S' J,;' J~I ~\ J4 J..;.15' t: .=.-l; ).?J")IJ c:iLoS" i y..).,..,.)1 ~l;

iJ'-.).,..,.)1 ~W;.s-)'.:.r- (.$~ J ~ 4i')i.s. Js- J~I) ~ .:>iu ~ f _pil; oT'- ~ ,",,~II.J"LiI.

) J- / i\?).H .,'Y o}.I.U ~~) J- / i\?).H y. .-'0 J J- / i'? J.H ,o-',yo ~

j5:J ('='-~'. .)JJ.J) -, A) ('='-~" .).w) .""""'I$J~ ~ J.t,.-} J-lA..J 'J- / i\? J.H T',"

Js- Jo1i. l.l % ',.. I$J~ }.:.r- Jii.:>15' (!!l;.;1J ~I I$JI l\ J\.I-~\ J p .:>i .A )) 'J'.,:I1 Js- ~JaJ\.:.r-

.i-ili l+A:,1.; ~\oS::..! t: ~! J ,:II f ()1 J;1' .=.-')i.s.lA:!1 J)). c..,...,jl ~ ,U) ,~JaJ\ .:r,;~ oJ..:.. ~}.;>.;. .~)..:.r- l+# ~I.!JJ; t: (!!l;.;1J Wly 4"IL, )" .=.-l...'J.AJ' .=.-.;t11 ,U) ,4"II).AJ\ "",I}~' J J.,s-.il' ..,.oS')\

v j">I..J') J."j15' ~?\ ~\ y'-,,"" Js- C~ l+A:,1.; ~\oS::..! JJ~\ ~JaJ' .=.-.;t1i LoS" ~ JL;..JJ ..:-o~' °J~

.If;t i y..).,..,.)\ ~l; flili

Two simple and sensitive spectrophotometric methods are described for the determination of nafcillinsodium in pure form, tablets and biological fluids. The first method (method I) is based on the reductionof ferric ions into ferrous ions in presence of o-phenanthroline by nafcillin sodium to form a highly stableorange-red ferroin chelate [Fe. (phenhY+, measured at 510 nm. Maximum color formation was obtainedthrough heating. The second method (method 2) is based on the reaction of nafcillin sodium as n . donorwith p-chloranilic acid (P-CA) as a It-acceptor to form an orange - red complex measured at 530 nm.Bear's law is obeyed in the ranges of 1.25-15 ILg mrl and 15-200 ILg mrl with limits of detection of 0.12ILg mrl and 3.611Lg mr! and correlation coefficients of 0.9999 (n = 9) and 0.9998 (n = 10) for methods Iand 2, respectively. The mean relative standard deviations (RSD%) of the results within day precision andaccuracy of them were ~ 1.9 % which confirmed the reproducibility of the assay technique. The optimumassay conditions and their applicability to the determination of the drug in tablets are described. Themethods results showed insignificant difference with those of a reference method. The first method wassuccessfully applied to the determination ofnafcillin sodium in spiked urine and plasma.

Keywords: Spectrophotometric; Nafcillin sodium; Tablets; Biological fluids; Ferric-phenanthroline complex; p-Chloranilic acid.

. To whom all correspondence should be addressed; E-mail: [email protected]

.

- ~

36 Nawal A.AI-Arfaj, Sawsan A.Abdel-Razeq and Aziza A. AI-Hoshan

t " , '"' ..

INTRODUCTION mg), magnesium stearate (6.5 mg) and talc (31.5mg) per tablet [26]. Ferric o-phenanthroline

Nafcillin sodium (I) is a semisynthetic p- mixture (Fe3+ - phen) was prepared by transferringlactamic antibiotic widely used in medicine as an 0.2 g of o-phenanthroline (Riedel de Aaen Co.,effective way of healing serious infections caused Germany, 99.5%) into a 100 ml volumetric flask,by staphilococus aureus due to its resistance to 2 ml of concentrated hydrochloric acid (BDH,penicillinase produced by these bacteriums; 38%) and 0,1"6 g of Fe (N03h.9 H2O (GRG) weretherefore, the determination of nafcillin is added and the volume was completed to the markextremely important [1,2]. Numerous analytical, with distilled water. A buffer solution of pH =procedures have been repo~~d for its 5.08 was prepared using 0.2 M of acetic aciddetermination in pure form, pharmaceutical (BDH) and 0.2 M of sodium acetate (BDH). 0.02preparations or in biological fluids. The USP M p-Chloranilic acid (P-CA) was prepared bypharmacopoeia [3] recommends an HPLC assay, dissolving 0.417g of p-CA (MERCK) in methanolfor the evaluation of its raw.material and dosage (BDH) in a 100 ml volumetric flask. Plasmaforms. Other reported methods for determination (UDITROL"N"), acetonitrile (MERCK) wereof nafcillin are based on different analytical used and urine samples were obtained fromtechniques including HPLC [4-7], HPLC / MS healthy volunteers.[8,9], LC [10-12], ion-pair LC [13], LC/MS[14,15], GC [16,17], MS [18], phosphorimetry Procedures:[19,20], fluorimetry [21-23] and spectrophoto- Recommended procedures for calibration:metry [24,25]. The present paper describes two For method 1:new, sensitive, accurate and rapid spectrophoto- Working solutions of different volumes (0.1metric methods for the determination of nafcillin -1.2 ml) of standard stock solution of nafcillinsodium in pure form, tablets and biological fluids. (125 ~g ml-l) were transferred into a series of20 -

ml test tubes. 1.5 ml of (Fe3+ - phen) mixture andEXPERIMENTAL 3 ml of acetate buffer solution (pH 5.08) were

added to each tube and shaked. The test tubesApparatus: were heated in a water bath at 80°C for 30 min,

A UV -VIS Spectrophotometer (Ultrospec cooled to room temperature and transferred,2100 pro/80-2112-21/Amersham Bioscience) with quantitatively the contents of each tube to a 10 mlquartz cells of 1.0 cm path length was used for the volumetric flask and the volume was completedAm.. determinations and all absorbance with water. The absorbance of the resultingmeasurements. orange-red solution is measured at 510 nm against

a blank solution treated similarly. CalibrationReagents and Materials: graph was prepared by plotting the absorbance

Analytical reagents grade chemicals, against the drug concentration over the rangessolvents of spectroscopic grade and double cited in Table 1 for nafcillin sodium.distilled water were used throughout. For method 2:

Double pure nafcillin sodium sample was Working solutions of different volumes inprovided by SIGMA Chemical Co., USA and used the range (0.4 - 4 ml) of standard stock solution ofas received. 125 ~g mr1 drug standard solution nafcillin (500 ~g mr1) were transferred into awas prepared in distilled water for method-l and series of 10 ml volumetric flask. The drug sample500 ~g mr1 drug standard solution was prepared is allowed to react with 1 ml of 0.02 Mp-CA andin methanol for method 2. Working standard the orange-red complex was producedsolutions were prepared by appropriate dilution immediately. The volumes were completed withimmediately before use. Tablets containing the methanol and the absorbance of each solution wasstudied drug were prepared as each tablet measured at 530 nm against a reagent blankcontaining 250 mg of nafcillin sodium and the solution. Calibration graph was prepared bytablet excipients: lactose (350 mg), starch (30

J. Saudi Chern. Soc., Vol. 12, No.1

.. --=.'"

Spectrophotometric Determination ofNafcillin Sodium in Pure Form, Tablets and Biological Fiuids 37

plotting the absorbance against the drug due to their sulfur content. This phenomenon wasconcentration over the ranges cited in Table 1. used in this study to determine nafcillin sodium by

a spectrophotometric method. This methodProcedure for tablets: depends on that a quantity of ferric ions was

Ten tablets were mixed and weighed. An reduced by the analysed antibiotic into ferrousaccurately weighed amount of the powder ions. Then the later reacted with o-phenanthrolineequivalent to 12.5 mg of nafcillin sodium was to yield the orange-red ferroin chelate with '-max

~ transferred into a beaker with 50 ml distilled 510 nm, Fig.I.e w~ter, sonicated for 5 min and filtered into a 100 The development of the color depends very ml volumetric flask, then completed to volume much on the reaction conditions. Therefore it is

with water to obtain a 125 ~g mrl standard very important to optimize the reaction conditions.solution. The above procedure for method 1 was The effect of pH on the absorbance of ferrointhen followed. The nominal content of the tablets chelate was studied over a range of 3.4-5.8. Fig 2was calculated from the corresponding calibration showed that the absorbance at 510 nm increasedgraph or using the regression equation. Also, an with increasing pH value up to 5.08, after which itamount equivalent to 25 mg of the drug was remained constant. From 2-5 ml acetate bufferweighed accurately and transferred into a 100 - ml (pH 5.08) was found to be sufficient for maximumbeaker with 50 ml methanol, sonicated for 5 min color - intensity.and filtered into a 50 ml volumetric flask. The The effect of volume of (Fe3+/ o-phen)volume was completed with methanol to get a 500 reagent was studied in the range 0.5-4 mi. The~g ml-' standard solution for method 2. The absorbance increased with increasing volume ofmethod of standard additions was followed for the reagent. Maximum color intensity was obtaineddetermination of nafcillin in tablets using the upon using 1.5 ml of (Fe3+/ o-phen) reagent asprocedure described above for method 2. shown in Fig.3.

Temperature greatly enhances the reaction.Procedure for biological Ouids: Different temperatures were tested, from 30-Procedure for spiked urine: IOO°C, using the water bath. 75-100°C gave

12.5 mg of nafcillin sodium was weighed maximum color intensity, 80°C was chosen as theaccurately and added to I ml urine in a 100 ml best temperature for the reaction as shown in Fig.volumetric flask. The spiked urine was diluted 4. The development of the color of the productwith water to obtain 125 ~g ml-1 of nafcillin was completed after 30 min in the water bath atsodium and the procedure for method 1 was then 80°C and remained stable for at least 24 hr.followed. Blank solution was prepared by treating Application of Job's [29] and molar ratio methodsthe antibiotic - free urine in the same manner. [30] indicated a molar ratio of donor to acceptor 1:

4 for nafcillin sodium (Figs. 5,6). The reactionProcedure for spiked plasma: pathway can be represented as shown in scheme 1.

12.5 mg of nafcillin sodium was added toIml of plasma followed by 1 ml acetonitrile and Method 2:centrifuged at 3000 rpm for 10 min. The x-acceptors react with basic nitrogenoussupernatant was diluted with water to the mark in compounds as n - donors to form charge transfera 100 ml volumetric flask to obtain a 125 ~g mrl complexes or radical anions according to thenafcillin sodium solution and the procedure for polarity of the solvent used [31]. The amino groupmethod 1 was followed against a blank solution in nafcillin represents the electron donor groupsimilarly treated antibiotic - free plasma. which is responsible for the formation of charge

transfer complexes with electron acceptors.RESULTS AND DISCUSSION Nafcillin sodium reacts with p-chloranilic

acid (P-CA) forming an orange red coloredMethod 1: product which exhibit absorption maxima at 530

Different betalactam antibiotics have well - nm, Fig. 7.known reducing characters [27,28] which may be

..

.J. Saudi Chern. Soc., Vol. 12, No.1

--J. ~


..,

0.500

~~

;..c~ {

=~..c-<

0.000

350.0 400.0 500.0 600.0 700.0Wavelength (nm)

Fig. 1: Absorption spectrum of ferroin chelate formed from the reaction of nafcillinsodium (10 Jig ml-1 with 1.5 ml of (Fe3+ / o-phen) in presence of buffersolution of pH 5.08 after heating at 80°C for 30 min.'

1.4

1.2aI 1

, ~1; .e 0.8

i 0.6-=< 0.4

0.20

3 35 4 45 5 5.5 6 6.5

pHFig. 2: Effect of pH of buffer solution on the absorbance of the formed ferroin chelate

at 510 nm , nafcillin sodium (10 Jig ml-1, (Fe3+ / o-phen) 1.5 ml, temperature80°C, heating time 30 min.


-- ~


1.4

1.2..-/ Q) 1

~ 0.8of~ 0.6

:. ~ 0.40.2 J

00 0.5 1 1.5 2 2.5 3 3.5 4 4.5

Volmm (mJ)

Fig. 3: Effect of volume of (Fe3+ / o-phen) reagent on the absorbance of ferroin chelateformed at 510 nm , nafcillin sodium (10 Jig ml-I), pH 5.08, temperature 80oC,heating time 30 min.

1.4

1.2

Q) 1u; 0.8..a-~ 0.6..ao=X 0.4

0.2

00 20 40 60 80 100 120

Tenperatme (C)Fig. 4: Effect of heating temperature on the absorbance of ferroin chelate formed at

510 nm, nafcillin sodium (10 Jig mrl), pH 5.08, heating time 30 min.

1.4

U

i I

0.8

1 0.6~ 0.4

0.1

00 0.1 U 0.3 0.4 o.~ 0.6 0.7 0.8 0.9 . Vrl(VD+V~

1 0.9 o.a 8.1 .., o.s O.~ 0.3 1.1 8.1 0 Va/{Vo+Va)

Fig. 5: Stoichiometry of the reaction of(6.154 x 10-3M) nafcillin sodium with (6.154x 10-3 M) Fe3+ / o-phen by Job's method, V D = volume of drug, V R = volume

of reagent.

,J. Saudi Chern. Soc., Vol. 12, No.1

~ -'"'7

40 Nawal A.Al-Arfaj, Sawsan A.Abdel-Razeq and Aziza A. Al-Hoshan

1.4

1.1

I

J :~-C

0.4

0.1

0. I 2 .1 . 5 , 1 . , 10 11 12 tJ

[88/ID )Fig. 6: Stoichiometry of the reaction of (6.154 x 10-3 M) nafcilIin sodium, IDJ,

with (6.154 x 10-3 M) Fe3+ / o-phen, IRI, by Molor ratio method.

NaO 0H3C""'0 0 0 ~N

i CH3..::tJ:: + 4Fe3+ + 4Jt~ S CH3

NafcilIin Sodium 1

~" NaO 0H3C""'0 0 0 ~ CH3N~ + 4Fe2+ + 4Jt~ s~ CH3~ "0

2+

12 + 4Fe2+ ~ 4 Fe

o-Phenanthroline Ferroin

Scheme (1): Reaction mechanism between NafcilIin Sodium and o-Phen/Fe3+


.. ~


, ""

0.300

Q)C,). ~ 0.200

.e

~ 0.100 \'"""

0.000

350.0 400.0 500.0 600.0 700.0

Wavelength (nm)Fig. 7: Absorption spectrum of the reaction product of nafcillin sodium(180 Jig ml-l)

with p-CA (O.OO2M) in methanol.

Since polar solvent is used (methanol), this radical anions [32,33]. The reaction may beband may be attributed to the formation of p-CA represented by the following equation:

0° + A ~ [Do A] ~ Do+ + AoDonor Acceptor Complex Radical ions

(Nafcillin Sod.) (P-CA)The reaction conditions were optimized with The effect of p-CA concentration was

regard to the nature of the solvent, the studied. Different volumes of 0.02 M p-CA in theconcentration of the reagent and the effect of time. range 0.5-3 ml were used. Maximum absorption

Water, ethanol and methanol were tried as was obtained upon using 1 ml of 0.02 M p-CAsolvents for the color formation and as diluents for with final concentration of 0.002 M of p-CA,the reaction products. Methanol alone was above which the absorption decreased as shown inessential for the color stability and quantitative Fig. 8.precise results. Ethanol decreases the absorbance Maximum color intensity at ambientof the product and water inhibits the reaction. temperature was attained immediately with p-CAMethanol is a good solvent for nafcillin sodium and remained stable for more than one hour.and p-CA as it affords maximum color intensity Application of molor ratio method [30] indicated aand has a fairly good solvating power for 7[- molar ratio of donor to acceptor I: 1 for nafcillinacceptors. sodium (Fig. 9).

,J. Saudi Chem. Soc., Vol. 12, No.1

,


0.180 .16 ~ ,0.14 """" -6 ~ 0.12

~ 0.1i 0.08,.c< 0.06

0.040.02

00 1 2 3 4 5 6 7

p-CA Concentration (M)Fig. 8: Effect of p-CA concentration on the absorbance of nafcillin sodium (90 Jig mrl)

/ p-CA complex at 530 nm.

1..1

I

U 0.8...cj 0.6

~ ...

0.1

00 U 1 1.5 2 1.5 3 3.'

(RVID)Fig. 9: Stoichiometry of the reaction of (0.01 M) nafcillin sodium, (D), with (0.01 M) p-

CA, (RJ, by Molar ratio method.

Determination of nafcillin sodium: ~g mrl for method I and 15-200 ~g mrl forUnder the described experimental method 2 as given in Table 1. The relative

conditions, standard calibration curves for standard deviations (%RSD) were 0.94% for 10nafcillin sodium by the two methods were ~g mr' nafcillin sodium in method I and 1.9% forconstructed by plotting the absorbance versus 40 ~g mrl in method 2 based on 10 replicateconcentration. Conformity to Beer's law was determinations of each method.evident over the concentration ranges of 1.25-15


'. ~~


Least - squares regression calibration curves Pharmaceutical Applications:of nafcillin sodium were found to be linear at the In order to evaluate the analytical usefulnessstudied concentration ranges with correlation of the proposed methods, they were applied to thecoefficients, r, of 0.9999 and 0.9998 for methods determination of nafcillin sodium in tablets. The1 and 2 respectively as shown in Table 1. It also results were listed in Table 2 and agreed well withshows the linear ranges used, the regression the reference method [24]. The results showedequations parameters, limits of detections and excellent recoveries were obtained. To ovoid the

" limits of quantitations for both methods 1 and 2. effect of the matrix interference by method 2, i. e.The precision of the proposed methods was reduction of the absorbance signal by other

. evaluated by analysing standard solutions of the sample components in tablets of nafcillin sodium,studied drug from replicate analysis (n = 3) at the method of standard additions was constructedconcentrations within the linear ranges of the two to overcome these interferences.methods for nafcillin sodium. The results in Table2 were in accord with those obtained by a Biological Ouids applications:reference method [24]. The high sensitivity attained by the proposed

Statistical analysis [34] of these results using method 1 allowed the determination of nafcillinthe Paired student's t-test and the variance ratio F- sodium in biological fluids. The drug can betest showed no significant difference between the directly analysed in urine without anyperformances of the methods as regards to pretreatment. However, for plasma only aaccuracy and precision. deproteination process was carried out using

Good reproducibilities were obtained upon acetonitrile, as a sample pretreatment; anapplication of the proposed methods to djfferent extraction procedure was not necessary. Resultsblind experiments of pure samples of nafcillin obtained are listed in Table 3, where thesodium; the mean accuracies were 100.1 :!: 0.49 recoveries of the studied drug are 99.6 and 94.5and 100.3 :!: 0.88 by Fe3+/o-phen and p-CA from urine and plasma respectively.methods respectively (Table 2).

Table 1: Performance data for spectrophotometric determination of nafcillin sodium with thementioned reagents

:. .Proposed methods usmg-Parameter - 3+'__L_- - -,",A-'

F + / h CA -' - --- --~~- ~ t-e- I o-pnen P;~~A max (nm) 510 530

Linearity range, (~g mrl) 1.25-15 15-200(n=9) (n= 10)

Regression equation:Intercept (a) -0.049 -0.032

Sa 0.003 0.002Slope (b) 0.130 0.002

Sb 0.00 0.00Correlation coefficient (r) 0.9999 0.9998

LOD(~gmrl) 0.12 3.61LOQ (~g mrl) 0.39 12.11% RSD (n=10) 0.94 1.9

Sa: Standard deviation of intercept.Sb: Standard deviation of slope.

r,

J. Saudi Chem. Soc., Vol. 12, No.1 [ .0...,[

"""'"'


Table 2: Determination of nafcillin sodium in pure form and tablets by the proposed and referencemethods.

-Preparation Fe3+ / o-phen Method p-CA Method Reference Method (24)- - . .

Pure nafcillin sodium% Found t S. D. 100.1 t 0.49 100.3 t 0.88 100.9 t 0.58

n=9t-value 0.78(2.145) 0.39(2.131)F - value 1.42 (3.58) 2.26 (3.37)

Nafcillin sodium tablets *

(250 mg / tablet)%RecoverytS.D. 100.ltO.49 100.4tO.75 100.26tO.46

t - value 0.25 (2.365) 0.198 (2.776)

F-value 1.14(5.79) 2.66(19) c. .

* Prepared tablets containing the drug and the tablet excipients: lactose (350 mg), starch (30 mg),

magnesium stearate (6.5 mg) and talc (31.5 mg) per tablet [26].Figures in parentheses are the theoretical t and F values at p = 0.05

Table 3: Determination of nafcillin sodium in spiked urine and plasma usingthe (Fe3+ / o-phen) reagent.

% RecoveryUrine Plasma100.3 92.0100.8 96.099.0 95.3

~" 98.3 94.7

Mean t S. D. 99.6t 1.15 94.5t 1.75

Conclusion: quality control. Method - I is more sensitive thanIn this work, both ferric - phenanthroline and method - 2 and can be applied to biological fluids.

p-chloranilic acid were found to be efficient A k I d th . fi h h . c now e gemen :i; romogernc reagents or t e spectrop otometnc Th th t fi I II th k th D h"

" . . . . e au ors grea e e u y an e eans IP

determInatIon of nafclllm sodIum. The two f d " h . K. S d U . .ty fi. 0 aca emlc researc In mg au nlverSI or

proposed methods are simple and have also the rt fth ' hd f h. h d . . . h suppo 0 IS researc .a vantages 0 Ig accuracy an precIsIon witlow detection limits compared with the published ~~ 0 spectrophotometric methods which involve I H H

heating the drug solution with ammonium ~ 'j:t::i iY CH3 vanadate [24] or ammonium molybdate [25] in INcH

acidic medium. The proposed methods are also ~ N, 3easier and cheaper to perform than HPLC 0 a tOO-Na+separations and do not require expensive reagents. IThese advantages coupled with acceptable H3c/precision make these methods suitable for routine (1)

J. Saudi Chem. Soc., Vol. 12, No. I

~ ~ -.""


REFERENCES [17] U. Meetschen and M. Petz, Z-LebensmUnters Forsch., 193 (4), 337 (1991).

[18] T. Goto, Y. Ito, S.Yamada, H. Matsumoto[I] S. Budavor, M.J. O'Neil, A. Smith, P.E. and H. Oka, J. Chromatogr- A, 1100 (2),193

Heckelman and J.F. Kinneary, The Merck (2005).Index, 12th edition, Merck Co., Inc., [19] J.A. Murillo-Pulgarin, A. Alanon-MolinaWhitehouse station, NJ, (1996). and M.T. Alaft6n-Pardo, Anal. Chim. Acta,

[2] J.E.F. Reynold, K, Parfitt, A. V. Parsons and 423 (1),85 (2000).- S.C. Sweetman, Martindale the Extra [20] A. Fernandez-Gonzalez, R. Badia and M.E.

. Pharmacopoeia, London, (1996). Diaz-Garcia Anal, Chim, Acta, 498 (1-2),[3] The United States Pharmacopoeia, The 69 (2003). '

National Formulary, Official from January I, [21] J.A. Murillo-Pulgarin, A. Alanon-Molina, P.(2000). Fernandez, A. Munoz and A. Espinosa-

[4] I. Katime, V. Saez and E. Hernaez, Polymer Mansilla, Analyst, 123,1073 (1998).Bulletin, 55 (6), 406 (2005). [22] J.A. Murillo-Pulgarin, A. Alanon-Molina,

[5] L. K. Sorenson and L. K. Snor, Talanta,41 (1),21 (1994).Chromatographia, 53, (7-8), 367 (2001). [23] J.A. Murillo-Pulgarin, A. Alanon-Molina,

[6] L. K. Sorenson and L. K. Snor, T. Elkaer and Anal. Lett., 26 (II), 2409 (1993).H. Hansen, J. Chromatogr. B: Biomed. [24] B. Morelli and M. Mariani, Anal. Lett., 20Appl., 734 (2), 307 (1999). (9), 1429 (1987).

[7] S. Taguchi, S. Yoshida, Y. T~naka and S. [25] B. Morelli, Anal. Lett., 20 (I), 141 (1987).Hori, Shokuhin Eiseigaku Zasshl, 40 (5),375 [26] H.A. Liebrman, J.L. Kanig and L. Lachman,

(1999). Theory and Practice of Industrial Pharmacy,[8] M. Silvia Diaz-Cruz, M. Jose L6pez de AIda 3 rd edition, Lippincott, Williams And

and d. Barcel6, Journal of Chromatogr A, Wilkins, (1986).1130, (1),72 (2006).. . [27] British Pharmacopoeia, Vol. I, The

[9] C.K. Fagerquist and A.R. Lightfield, Rapid Stationary Office, London P 274, 275Commun. Mass Spectrom., 17 (7), 660 (1998).(2003). [28] M.I. Walash, S. Toubar, S.M. Ahmad and

[10] E. Benito-Pefta, A.I. Partal-Rodera, M.E. N.A. Zakhari; Anal. Lett., 27 (13), 2499Le6n-Gonzalez and M.C. Moreno-Bondi., (1994).Anal. Chim. Acta, 556 (2), 415 (20.06) [29] R. Foster "Organic Charge Transfer

[I I] E. Verdon, P. Coueder, P. Maris and M. Complexes" Academic Pr~ss, London,Laurentie, J. AOAC Int., 85 (4),889 (2002). England (1969).

[12] R.L. Earley, J. S. Miller and L.E. Welch, [30] S. Belal" Analyst, 111, 1039 (1988).Talanta, 45 (6),1255 (1998).. [31] M. E. Abdel-Hamid, M. Abdel-Salam, M.S.

[13] K. Takeba, K. Fujinuma, T. Miyazaki and H. Mahrous and M.M. Abdel- Khalek, Talanta,Nakazawa, J. Chromatogr. A, 812 (1-2), 205 32,1002 (1985).(1998). [32] J. Rose, "Advanced Physico - Chemical

[14] Y. Ito, T. Goto, H. Oka, H. Matsumoto and Experiments", Pittman, London, P 54 (1964).K. Takeba, J. Chromatogr- A, 1042 (1-2), [33] C.N.R Roa, S.N. Bhat and P.C. Dwined107 (2004). "Applied Spectroscopy Reviews" Brame EG,

[15] E. Daeseleire, H. de Ruyck and R. van Vol. 5. Marcel Dekker, New York P. 1170Renterghem, Rapid Commum. Mass (1972).Spectrom., 14 (15),1404 (2000). [34] J.C.Miller, J.N.Miller, Eds. "Statistics in

[16] U. Meetschen and M. Petz, J. Assoc. OtTo Analytical Chemistry". John Wiley, NewAnal. Chern., 73 (3),373 (1990). York, (1983).

.J. Saudi Chern. Soc., Vol. 12, No. I

~jaj' vi .~4 .:>.,ij1 ':>:;:;~) 'p yl; 0' j~ -...

Documents