The Chi nese Phar ma ceu ti cal Jour nal, 2003, 55, 481-490

481

Spectrophotometric Determination of Aciclovir, Ceftazidime Pentahydrate, Famotidine and Isoxsuprine Hydrochloride by Ternary Complex Formation with Eosin and Cu(II)
Marwa S. Elazazy*, Abdalla Shalaby, M. N. Elbolkiny and Hawa M. Khalil
An a lyt i cal Chem is try De part ment, Fac ulty of Phar macy, Zagazig Uni ver sity, Zagazig, Egypt (Received November 14, 2003; Ac cepted February 16, 2004)

ABSTRACT
A sim ple, rapid and sen si tive spec tro pho to met ric method has been de scribed for the de termina tion of aciclovir, ceftazidime pentahydrate, famotidine and isoxsuprine hy dro chlo ride based o n ter nary com plex for ma tion with eosin and Cu(II). The method does not in volve sol vent ex traction. The col our of the pro duced com plex is mea sured at 545-548 nm. Ap pro pri ate con di tions were es tab lished for the col our re ac tion and for the drug:Cu(II): eosin ra tio to ob tain max i mum se n si tivity. Un der the pro posed con di tions this method is ap pli ca ble over con cen tra tion range of 1-35 g -1 3 5 -1 -1 mL with mo lar absorpitivities rang ing from 7.283 10 - 1.182 10 L.mol .cm and Sandell sen-3 -3 -2 si tiv i ties rang ing from 2.847 10 - 9.9016 10 g cm . The re sults ob tained dem on strated that the pro posed method is equally ac cu rate, pre cise and re pro duc ible as the of fi cial or re po rted methods, and thus it is rec om mended for qual ity con trol and rou tine anal y sis where time, cost ef fec tiveness and high spec i fic ity of an a lyt i cal tech niques are of great im por tance. Key words: Spectrophotometry; Ter nary com plex; Eosin; Cu(II); Dosage forms.

INTRODUCTION
Aciclovir is an an ti vi ral agent thats cur rently used in treat ment of Herps vi rus in fec tion (type I and II).1 It has been de ter mined by sev eral pro cedures e.g. spectrophotometry,2,3 HPLC4-7 and ra di oimmunoassay. 8 Ceftazidime pentahydrate is a third gen er a tion cephalosporin thats used both orally and par enterally. 1 Sev eral pro ce dures were pro posed for its de ter mi na tion e.g. spectrophotometry,9-11 HPLC,12-14 polarography, 15 voltammetry16 and ELISA.17 Famotidine is an H2-re cep tor an tag o nist thats

used in treat ment of gas tric and du o de nal ul cers.1 Sev eral pro ce dures were per formed for its de ter mination e.g. spectrophotometry,18-20 HPLC, 21-23 potentiometry24 and voltammetry.25 Isoxsuprine hy dro chlo ride is a -adrenoceptor ag o nist thats now used in treat ment of navicular disease. 1 Methods sug gested for its de ter mi na tion include spectrophotometry, 26-28 HPLC29 and voltammetry. 30 The pur pose of this study was to de ter mine the four drugs in their pharmaceutical prep arations with out prior ex trac tion by sim ple, rapid and se lective as says for qual ity con trol and rou tine anal y sis

482

Chin. Pharm. J. Vol. 55, No. 6, 2003

Elazazy et al.

pur poses based on ter nary com plex for ma tion between the stud ied drug-metal ion [Cu(II) (drug)n] as cat ion and an or ganic dye (eosin) as an ion.

EXPERIMENTAL Apparatus
A Shimadzu 260-UV re cord ing spectro photometer with 10 mm quartz cell was used for all absorbance mea sure ments.

Materials and reagents

All chemicals were of an alytical grade and dou bly dis tilled wa ter was used through out all measurements. 1- Pure drug sam ples were kindly sup plied by Mem phis Co. for Pharm. Ind., Cairo, Egypt ex cept for ceftazidime pentahydrate which was sup plied by T3A Phar ma ceu ti cals, Assuit, Egypt. 2- Eosin (Sigma, Aus tria), 0.1% w/v, aque ous so lu tion, sta ble for 2 weeks. 3- Cop per(II) chlo ride (Merck, Ger many), 0.2 and 0.3% w/v aque ous so lu tions. 4- So dium lauryl sul phate (SLS) (Merck, Germany), 0.1 and 0.2% w/v aque ous so lu tions.

2- Fortum vi als; (2 gm ceftazidime penta hydrate per vial), Glaxo Wellcome, Greenford, England. 3- Famotin tab lets; (20 mg famotidine per tab let), Memphis Co. for Pharm. & Chem. Ind., Cairo, Egypt. 4- Gastrodomina 20 tab lets; (20 mg fa motidine per tablet), MUP, Abu-Sultan, Ismailia, Egypt. 5- Novirus cap sules; (200 mg aciclovir per cap sule), Galxo Wellcome Egypt, Cairo, Egypt. 6- Zovirax vi als; (250 mg aciclovir Na per vial), The Wellcome for mu la tion, Ltd., Eng land. 7- Duvadilan tab lets; (20 mg isoxsuprine HCl per tablet), Pharco Pharm., Alexandria, un der licence of Sol vay Pharm. B. V., WEESP, Hol land. 8- Vascular tab lets; (20 mg isoxsuprine HCl per tab let), SEDICO, 6 Oc to ber city, Egypt.

Procedure
For pure pharmaceuticals Ac cu rately mea sured aliquots of the stan dard drug so lu tions rang ing from 10-350 g mL -1 were trans ferred into sep a rate 10 mL vol u met ric flasks, and then add 0.5-1 mL aliquots of 0.1%-0.2% w/v SLS to each flask fol lowed by 1 mL of 0.2-0.3% w/v Cu(II) so lu tion and 1 mL of 0.1% eosin so lution (Table 1). The con tents of each flask were shaken thouroghly and each mix ture was di luted to 10 mL with dis tilled wa ter. The flasks were left at room tem per a ture for 5-10 min utes, and then the absorbance was mea sured at the spec i fied wavelength (Ta ble 1). For pharmaceutical formulations (A) For vials The con tents of 2 vi als were mixed well, an amount equiv a lent to 100 mg of the ac tive in gre dient was trans ferred into 100 mL vol u met ric flask and the vol ume was made up to the mark with dis-

Standard drug solution

Stock so lu tions of 1 mg mL -1 were pre pared by dis solv ing 100 mg of the drug sub stance in 100 mL dis tilled wa ter (heat ing in boil ing wa ter bath for 2 min. is ap plied in case of aciclovir, famotidine and isoxsuprine HCl).

Formulations
The fol low ing com mer cial for mu la tions were sub jected to the an a lyt i cal pro ce dures: 1- Cetazim vials; (642 mg ceftazidime pentahydrate so dium car bon ate mix ture equiv alent to 500 mg ceftazidime per vial), T3A, Assuit, Egypt.

Spec tro pho to met ric De ter mi na tion

Chin. Pharm. J. Vol. 55, No. 6, 2003

483

Table 1. Analytical Data for Determination of Investigated Drugs Drug 1-Aciclovir 2-Ceftazidime.5H2 O 3-Famotidine 4-Isoxsuprine HCl max (nm) 547 545 547 547 Reaction time (min.) 5 10 5 5 Concentration (%) & Volume (mL) of SLS 0.1%-1 mL 0.2%-1 mL 0.1%-0.5 mL 0.1%-1 mL Concentration (%) & Volume (mL) of Cu(II) 0.2%-1 mL 0.3%-1 mL 0.2%-1 mL 0.3%-1 mL Concentration (%) & Stability Volume (mL) (h) of eosin 0.1%-1 0.1%-1 0.1%-1 0.1%-1 mL mL mL mL 1 3 2 1

tilled wa ter. Drug con tent in the ob tained so lu tion was de ter mined fol low ing the gen eral pro ce dures. (B) For tablets Ten tablets of each of famotidine and iso xsuprine hy dro chlo ride were ac cu rately weighed and ground into a fine pow der. A weight of pow der equiv a lent to 100 mg of the drug was trans ferred into 100 mL vol u met ric flask and dis solved in 60 mL wa ter by aid of heat ing in boil ing wa ter bath for 2 min. The so lu tion was cooled and fil tered into 100 mL cal i brated flask. The fil ter was washed with distilled wa ter, and then the vol ume was made up to 100 mL with water. The drug content in the obtained ex tract was de ter mined fol low ing the general pro ce dures. (C) For capsules The con tents of twenty cap sules were emp tied and a known weight of the pow der equiv a lent to 100 mg of the drug was trans ferred into 100 mL volu met ric flask and dis solved in 60 mL dis tilled wa ter by aid of heat ing. Com plete as de scribed un der tablets and fol low the gen eral pro ce dures.

RESULTS AND DISCUSSION

The main pur pose of this study was to es tablish a sim ple spec tro pho to met ric method for the deter mi na tion of some phar ma ceu ti cally in ter est ing com pounds in their dos age forms with out prior extrac tion. The pro posed method us ing ter nary complex for ma tion with eosin and Cu(II) is de scribed.

Ter nary com plexes formed be tween the metal ion:electronegative ligand and an or ganic base often have higher val ues of mo lar ex tinc tion co ef ficient than or di nary (dou ble) com plexes of the same com po nents. The for ma tion of ter nary com plexes was re ported to im prove not only the sen si tiv ity but also the se lec tiv ity as well. A typ i cal fea ture is that in ter nary com plexes the third com po nent does not weaken the bond be tween the first two, but sometimes even re in forces the sta bil ity of the com plex.31 The ab sorp tion spec tra of the ter nary com plex (drug - Cu - eosin) were scanned in the range of 430-630 nm against a re agent blank, and char ac teris tic ab sorp tion max ima at 545-547 nm were observed (Fig. 1). To op ti mize the as say pa ram e ters, the ef fects of pH, se quence of additon of the re ac tants, re ac tion time, tem per a ture, concentration of surfactant, eosin and cop per(II) chlo ride on the absorbance of the ter nary com plex formed with re spect to max imum sen sitivity, min imum blank, adher ence to Beers law and sta bil ity were stud ied through control ex per i ments. The op ti mum con di tions were estab lished by vary ing one vari able and ob serv ing its ef fect on the absorbance of the col oured prod ucts. The ef fect of pH on the absorbance of ter nary com plex was studied using acetate buffer of pH value (2-6). No marked dif fer ence in absorbance and sen si tiv ity was ob served so there was no need to add buffer so lu tion. In or der to ex am ine the ef fect of tem per a ture

484

Chin. Pharm. J. Vol. 55, No. 6, 2003

Elazazy et al.

and re ac tion time on the absorbance of the ter nary com plex, the above men tioned pro ce dure was carried out at dif fer ent tem per a tures (room tem per ature, 50, 60, 70 and 80 C) us ing ther mo static wa ter bath. Max i mum and con stant absorbance was obtained at room tem per a ture (25 5 C) and by waiting for 5-10 min utes af ter di lu tion (Fig. 2). The ef fect of surfactant on the absorbance of the so lu tion of the com plex was stud ied us ing var ious dis pers ing agents, for ex am ple the cationic surfac tants benzalkoniuim chlo ride and cetrimide, the an ionic surfactant so dium lauryl sul phate and the non-ionic surfactants tween 20, 80 and hydroxy propyl methyl cellu lose. Among the sur fac tants stud ied the best re sults were ob tained in the pres0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 450

ence of so dium lauryl sul phate (SLS), and max imum and con stant absorbance was ob tained with 0.5-1 mL of 0.1%-0.2% w/v SLS (Fig.3). In this study addition of so dium lauryl sul phate was found to be nec es sary for com plex sta bility and pre ven tion of pre cip i tate for ma tion. Con cern ing the ef fect of eosin con cen tra tion on the absorbance of the com plex formed, the op timum re sults were ob tained us ing 1 mL of 0.1% w/v eosin (Ta ble 1 and Fig. 4). Also the ef fect of Cu(II) chlo ride con cen tration was stud ied by keep ing the con cen tra tion of eosin and surfactant con stant and vary ing the metal con cen tra tion. Op ti mum re sults were ob tained by us ing 1 mL of 0.2%-0.3% w/v cop per chlo ride (Ta-

Aciclovir Ceftazidime pentahydrate Famotidine Isoxsuprine hydrochloride

Wavelength (nm)
500 550 600 650

Fig. 1. Absorption spectra of reaction products: Fig. 1. Ab sorp tion spec(1) 20 g acml aciclovir. (1) 20 g/mL aciclovir. (2) 28 g/mL2ceft azi dime.5H2O. (3) 5 g/mL tra of re / tion prod ucts: (2) 28 g / ml ceftazidime.5H O. famotidine. (4) 20 g/mL ml famotidine. (3) 5 g / isoxsuprine HCl. (4) 20 g / ml isoxsuprine HCl.
0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Reaction time (min.)

Aciclovir Ceftazidime pentahydrate Famotidine Isoxsuprine hydrochloride

0 10 20 30 Fig.2. Effect of reaction time : Fig. 2. Ef fect of re ac tion time: (1) 20aciclovir. (1) 20 g / ml g/mL aciclovir. (2) 28 g/mLml ceftazidime.5H2O. 5 g/mL famotidine. (4) 20 (2) 28 g / ceftazidime.5H2O. (3) g/mL iso x su prine 5 g / ml famotidine. (3) HCl. (4) 20 g / ml isoxsuprine HCl.

Spec tro pho to met ric De ter mi na tion

Chin. Pharm. J. Vol. 55, No. 6, 2003

485

ble 1 and Fig. 5). The ef fect of or der of ad di tion of the re ac tants
0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0

was also stud ied. It was found that putt ing drug, surfactant, metal and then eosin gave the best re-

Aciclovir Ceftazidime pentahydrate Famotidine Isoxsuprine hydrochloride

Volume of surfactant (ml)

Fig. 3.

0 0.5 1 1.5 2 2.5 Fig.3. Effect of surfactant volume : Ef fect of surfactant vol ume: (1) 20 g/mL aciclovir. (2) 28 g/mL ceftazidime.5H2O. (3) 5 g/mL famotidine. (4) (1) 20 g / ml aciclovir. (2) 28 g / ml ceftazidime.5H 2O. 20 g/mL isoxsu prine HCl. famotidine. (3) 5 g / ml (4) 20 g / m l isoxsuprine HCl.

0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 E osin volume (ml) 0 1 2 3 Fig.4. Effect of eosin volume : Ef fect of eosin vol ume: (1)ml aciclovir. (1) 20 g / 20 g/mL aciclovir. (2) 28 g/mL ceftazidime.5H22O. (3) 5 (2) 28 g / ml ceftazidim e.5H O. g/mL iso xsuprine 5 g / ml fam otidine. (3) HCl. (4) 20 g / ml isoxsuprine HCl.

Aciclovir Ceftazidime pentahydrate Famotidine Isoxsuprine hydrochloride

Fig. 4.

g/mL famotidine. (4) 20

0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 CuCl2 volume (ml) 1 2 3 Fig.5. Effect of CuCl2 volume : Ef fect of CuCl 2(1) 20 g /(1) 20 g/mL aciclovir. (2) 28 g/mL ceftazidime.5H2O. (3) 5 g/mL famotidine. (4) 20 vol ume: ml aciclovir. (2) 28 g / ml ceftazidime.5H2O. g/mL iso xsuprine HCl.ml famotidine. (3) 5 g / (4) 20 g / ml isoxsuprine HCl. 0 0

Aciclovir Ceftazidime pentahydrate Famotidine Isoxsuprine hydrochloride

Fig. 5.

486

Chin. Pharm. J. Vol. 55, No. 6, 2003

Elazazy et al.

sults in stead of any other or ders of ad di tion. The col our ob tained was found to be sta ble for at least 1 hour at room tem per a ture (Ta ble 1).

Constitution of the complex

The nature of the complex (drug - metal eosin) was de ter mined us ing jobs method of continuous variation. The results of ap plying this method can be summrerized as fol lows: The Cu(II): drug ra tio in the pres ence of ex cess eosin was 1:1 in the case of aciclovir, ceftazidime, famotidine and 2:1 in the case of isoxsuprine HCl while Cu(II): eosin ra tio in pres ence of ex cess drug was 1:1 for all in ves ti gated drugs. On the other hand drug:eosin ratio in pres ence of ex cess Cu(II) was 1:1 in the case

of aciclovir, ceftazidime and famotidine and 2:1 in the case of isoxsuprine HCl so drug: Cu(II): eosin ra tio in pres ence of surfactant was 1:1:1 in the case of aciclovir, ceftazidime and famotidine and 2:1:1 in the case of isoxsuprine HCl.

Calibration graphs
A lin ear cor re la tion was found be tween absorbance and con cen tra tion in the range given in Ta ble 2. The cor re la tion co ef fi cients, in ter cepts and slopes for the cal i bra tion data for the tested drugs were cal cu lated us ing least-squares method.

Quantification, Accuracy and Precision

The mean Sandell sensitivity and mo lar ab-

Table 2. Optical Characteristics for the Reaction of Cited Drugs with Cu(II)-eosin Drug 1-Aciclovir 2-Ceftazidime.5H 2O 3-Famotidine 4-Isoxsuprine HCl Beers Law Limits (g mL-1) 2.5-35 4-30 1-8 5-23 Molar absorpitivity (L.mol-1 .cm-1) 0.7283 10 4 1.813 10 4 3.3413 104 1.182 10 4 Sandell sensitivity (g cm-2) 3.234 10 -3 2.847 10 -3 9.902 10 -3 3.502 10 -3 R* 0.999999 0.99999 0.99998 0.99998 b* 0.02301 0.0273 0.0956 0.0355 a* 0.08171 0.01204 9.955 10 -3 -4.949 10 -3

* Regression equation: -A = a + bc a = intercept, b = slope, c = concentration (g mL -1 ), A = absorbance unit Table 3. Comparative Analytical Results of the Proposed and the Reported Methods for the Tested Drugs in Pure Forms Statisical Parameters** Mean % recovery N Variance S.D. S.E. R.S.D. t F
**

Aciclovir Proposed method 99.96 Official method32 99.94

Ceftazidime.5 H 2O Proposed method 99.99 Reference method 9 100.4 5 0.185 0.430 0.192 0.428

Famotidine Proposed method 99.81 5 0.262 0.512 0.229 0.513 0.401 (2.447) 2.339 (6.94) Official method 32 99.69 3 0.112 0.335 0.193 0.336

Isoxsuprine HCl Proposed method 99.96 5 0.093 0.305 0.136 0.305 1.609 (2.447) 1.710 (6.94) Official method32 99.53 3 0.159 0.398 0.230 0.400

6 3 8 -3 0.033 7.6 10 0.077 0.181 0.087 0.277 0.074 0.050 0.098 0.181 0.087 0.277 0.224 (2.365) 1.902 (2.306) 4.34 (5.79) 2.403 (5.14)

N = Number of experiments, S.D. = Standard Deviation, S.E. = Standard Error, R.S.D. = Relative Standard Deviation, F = Variance test, t = t test of unpaired data

Spec tro pho to met ric De ter mi na tion

Chin. Pharm. J. Vol. 55, No. 6, 2003

487

Table 4. Comparative Analytical Results of the Proposed and the Reported Methods for Tested Drug in Some Pharmaceutical Formulations Proposed method Formulation 1Zovirax vials Statistical parameters Mean % recovery N Variance S.D. S.E. R.S.D. t F Mean % recovery N Variance S.D. S.E. R.S.D. t F Mean % recovery N Variance S.D. S.E. R.S.D. t F Mean % recovery N Variance S.D. S.E. R.S.D. t F Mean % recovery N Variance S.D. S.E. R.S.D. t F Mean % recovey N Variance S.D. S.E. R.S.D. t F
**

Calibration method 100.75 5 0.225 0.474 0.212 0.470 0.997 (2.306) 2.5 (6.39) 100.65 5 0.096 0.310 0.139 0.308 1.068 (2.447) 1.25 (6.94) 100.78 6 0.299 0.547 0.223 0.543 0.443 (2.262) 2.534 (5.19) 99.92 6 0.425 0.652 0.266 0.653 0.222 (2.262) 1.426 (5.19) 99.6 5 0.839 0.916 0.410 0.920 0.337 (2.447) 1.265 (6.94) 99.99 5 0.163 0.404 0.181 0.404 0.339 (2.447) 1.00 (6.94)

Standard addition method 100.82 5 0.094 0.306 0.137 0.307 1.669 (2.306) 1.044 (6.39) 100.65 5 0.080 0.283 0.127 0.281 1.097 (2.447) 1.5 (6.94) 100.99 6 0.138 0.428 0.175 0.424 0.386 (2.262) 1.551 (5.19) 99.95 6 0.368 0.607 0.248 0.607 0.144 (2.262) 1.235 (5.19) 99.07 5 0.599 0.774 0.346 0.781 0.548 (2.447) 1.107 (6.94) 100.31 5 0.118 0.344 0.154 0.343 0.788 (2.447) 1.381 (6.94)

Reference method 100.532 5 0.090 0.300 0.134 0.299 100.39 32 3 0.120 0.346 0.200 0.345 100.99 5 0.118 0.344 0.154 0.341 100.00 5 0.298 0.546 0.244 0.546
9

2Novirus capsules

3Cetazim vials

4Fortum vials

5Famotin tablets

99.3924 3 0.663 0.814 0.470 0.819

6Gastrodomina 20 tablets

100.09 24 3 0.163 0.404 0.233 0.404

488

Chin. Pharm. J. Vol. 55, No. 6, 2003 7Duvadilan tablets Mean % recovery N Variance S.D. S.E. R.S.D. t F Mean % recovery N Variance S.D. S.E. R.S.D. t F 99.97 5 0.618 0.786 0.352 0.786 1.375 (2.306) 4.066 (6.39) 99.56 5 0.537 0.733 0.328 0.736 1.519 (2.306) 1.417 (6.39) 100.06 5 0.483 0.695 0.311 0.695 1.263 (2.306) 3.178 (6.39) 100.17 5 0.292 0.540 0.241 0.539 0.109 (2.306) 1.298 (6.39)

Elazazy et al. 100.51 26 5 0.152 0.390 0.174 0.388 100.21 26 5 0.379 0.616 0.275 0.615

8Vascular tablets

**

N = Number of experiments, S.D. = Standard Deviation, S.E. = Standard Error, R.S.D. = Relative Standard Deviation, t = t test of unpaired data, F = Variance test

sorp itivity for each drug were cal cu lated, and the ob tained val ues are listed in Ta ble 2. The pre ci sion and ac cu racy of the pro posed method were tested by means of rep li cate mea surements of the tested drugs within Beers law lim its. The % S.D and % range of S.E. at 95% con fi dence lim its are given in Ta ble 3 and Ta ble 4. The utility of this method was veri fied by means of rep li cate mea sure ments of phar ma ceu tical for mu la tions and re cov ery ex per i ments. Re coveries were de ter mined ei ther by add ing stan dard drug to a preanalysed mix ture of phar ma ceu ti cal prep a ra tion stan dard ad di tion tech nique or by apply ing the cal i bra tion method. The per for mance of the pro posed method was as sessed by cal cu la tion of t and F-values compared with of fi cial and ref er ence meth ods, and results showed that no sig nif i cant dif fer ence in ac curacy and pre ci sion be tween both meth ods. Also this in di cates a good reproducibility and re peat abil ity.

method is sim ple, ac cu rate and sen si tive with good pre ci sion and ac cu racy. With this method, one can do the anal y sis with speed at low cost and with out los ing ac cu racy. The pro posed method can be used as al ter na tive to the re ported ones for rou tine de termi na tion of these drugs in pure form and in phar maceutical prep a ra tions. This en cour ages their success ful use in routine anal ysis of these drugs in qual ity con trol lab o ra to ries.

REFERENCES
1. Martindale, The Complete Drug Reference, 32nd ed., 1999. 2. Mahrous, M. S.; Abdel-Khalek, M. M.; Daabees, H. G.; Beltagy, Y. A. Use of dif fer ential spectrophotometry for determination of cytarbine and aciclovir in their dos age forms. Anal. Lett. 1992, 25(8), 1491-1501. 3. Daabees, H. G. The use of de riv a tive spectrophotometry for the de ter mi na tion of acyclovir and diloxanide furoate in pres ence of im pu rity or deg ra da tion prod uct. Anal. Lett. 1998, 31(9), 1509-1522.

CONCLUSION
The data given be fore re veal that the pro posed

Spec tro pho to met ric De ter mi na tion

Chin. Pharm. J. Vol. 55, No. 6, 2003

489

4. Cronqvist, J.; Nilsson-Ehle, I. De ter mi na tion of acyclovir in human se rum by high per formance liq uid chro ma tog ra phy. J. Liq. Chromatogr. 1988, 11(12), 2593-2601. 5. Boulieu, R.; Gal lant, C.; Silberstein, N. De termi na tion of acyclovir in human plasma by high- performance liq uid-chromatography. J. Chromatogr. B:Biomed. Appl. 1997, 693(1), 233-236. 6. Xu, Y.; Zhou, S. W.; Tang, J. L.; Huang, L. Q. Determination of acyclovir in mouse plasma and tis sues by re versed phase high- per formance liq uid chro matography. Sepu 2001, 19(6), 538-540. 7. Loregian, A.; Gatti, R.; Palu, G.; de-Palo, E. F. Sep a ra tion meth ods for aciclovir and re lated anti-viral com pounds. J. Chromatogr. B:Biomed. Appl. 2001, 764(1-2), 289-311. 8. Tadepalli, S. M.; Quinn, R. P. Scintil la tion prox im ity radiommunoassay for the mea surement of acyclovir. J. Pharm. Biomed. Anal. 1996, 15(2), 157-163. 9. Amin, A. S.; Khalil, H. M.; Saleh, H. M. Spectrophotometric estimation of cefuroxime and ceftazidime in bulk and dosage forms. Sci. Pharm. 2001, 69, 143-150. 10. Saleh, G. A.; Askal, H. F.; Radwan, M. F.; Omar, M. A. Use of charge-transfer com plexation in the spec tro pho to met ric anal y sis of certain cephalosporins. Talanta 2001, 54(6), 1205-1215. 11. Saleh, G. A.; Askal, H. F.; Refaaet, I. H.; Mohamed, N. A. New re dox spec tro pho to metric meth ods for the analysis of cer tain cephalosporins through formazan for ma tion. S.T.P. Pharm. Sci. 2002, 12(2), 133-137. 12. Chan, C. Y.; Chan, K.; French, G. L. Rapid high-performance liq uid-chromatographic assay of cephalosporins in bi o log i cal flu ids. J. Antimicrob. Chemother. 1986, 18(4) , 537-545.

13. Barnes, A. R. De ter mi na tion of ceftazidime and pyridine by HPLC: ap pli ca tion to a vis cous eye drop formulation. J. Liq. Chromatogr. 1995, 18(15), 3117-3128. 14. Favetta, P.; Janoly, A.; Allombert, C.; Breysse, C.; Guitton, J.; Bu reau, J. Si mul ta neous quan tifi ca tion of ceftazidime and pyridine, its main degradation prod uct, by HPLC. Anal. Lett. 2000, 33(12), 2465-2475. 15. Reddy, G. V. S.; Reddy, S. J. Estimation of cephalosporin an ti bi ot ics by dif fer en tial pulse polarography. Talanta 1997, 44(4), 627-631. 16. Ferreira, V. S.; Zanoni, M. V. B.; Fogg, A. G. In di rect cath odic-stripping voltammetric de termi na tion of ceftazidime as a mer cury salt. Anal. Chim. Acta 1998, 367(1-3), 255-259. 17. Farrel, C.; Rowell, F. J.; D ilva, C.; Cumming, R. H. En zyme-linked immunosorbent as say for ceftazidime in airbrone sam ples. Analyst 1994, 119(11), 2411-2416. 18. Guvener, B.; Ates, S. Method for the as say of famotidine in tab lets. Acta Pharm. Turc 1988, 30(2), 67-68. 19. El-Yazbi, F. A. Sec ond-derivative spec tro photometric determination of famotidine. Spectrosc. Lett. 1992, 25(7), 1011-1021. 20. Li, H.; Xuan, J. UV spectrophotometry of famotidine tablets. Zhongguo Yiyao Gongye Zazhi 1993, 24(7), 319-321. 21. Rahman, A.; Hoffman, N. E. High- performance liq uid-chromatographic de ter mi na tion of famaotidine in urine. J. Chromatogr. Biomed. Appl. 1988, 72(2(J. Chromatogr., 428)), 395-401. 22. Cakir, B.; Tosun, A. U.; Sahin, M. F. Quan ti tative high-per for mance liq uid chro mato graphic anal y sis of famotidine in dos age forms. Pharm. Sci. 1997, 3(10) , 493-495. 23. Tahboub, Y. R.; Zaater, M. F.; Najib, N. M. Reversed-phase liq uid chro mato graphic method

490

Chin. Pharm. J. Vol. 55, No. 6, 2003

Elazazy et al.

for the de ter mi na tion of famotidine in se rum. Quim. Anal. 1998, 17(3), 117-120. 24. Petkovic, J.; Minic, D.; Koricanac, Z.; Jovanovic, T. Potentiometric de ter mi na tion of famotidine in phar maceutical dosage forms. Pharmazie 1998, 53(3), 163-164. 25. Squella, J. A.; Rivera, C.; Lemus, I.; Nunez-Vergara, L. J. Differential pulse voltammetric determination of famotidine. Mikrochim. Acta 1990, I(5-6), 343-348. 26. Sane, R. T.; Nayak, V. G.; Malkar, V. B. Sim ple spec tro pho to met ric method for the de ter mi nation of nylidrin hy dro chlo ride, isoxsuprine hydro chlo ride and sal buta mol sul phate in phar maceutical preparations. Talanta 1985, 32(1), 31-33. 27. Guneri, T.; Sevgi, F. Spec tro pho to met ric de termi na tion of isoxsuprine hy dro chlo ride. Acta Pharm. Turc. 1988, 30(3), 129-131. 28. Reddy, M. N.; Sankar, D. G. Spec tro pho to metric de ter mi na tion of isoxsuprine and nylidrin in

29.

30.

31.

32.

pharmaceutical preparations. In dian Drugs 1996, 33(8), 420-422. Hashem, A.; Lubczyk, B. Determination of isoxsuprine in equine plasma by High-per formance liq uid-chromatography with elec trochemical detection. J. Chromatogr. Biomed. Appl. 1991, 101(1(J. Chromatogr., 563)), 216-223. Belal, F.; Al-Malaq, H. A.; Al-Majed, A. A. Voltammetric de ter mi na tion of isoxsuprine and fenoterol in dos age forms and bi o log i cal flu ids. J. Pharm. Biomed. Anal. 2000, 23(6), 10051015. Kelani, K.; Bebawy, L. I.; Abdel-Fattah, L. Determination of astemizole, terfenadine and flunarizine hy dro chlo ride by ter nary com plex for ma tion with eosin and lead(II). J. Pharm. Biomed. Anal. 1999, 18, 985-992. Brit ish Phar ma co peia, The Sta tion ary Of fice, Lon don 1998.