DEVELOPMENT AND VALIDATION OF SPECTROPHOTOMETRIC DETERMINATION OF CEFPODOXIME PROXETIL IN PURE AND TABLET DOSAGE FORMS THROUGH ION-PAIR COMPLEX FORMATION USING BROMOTHYMOL BLUE Original Article ABDUL AZIZ RAMADAN 1* , HASNA MANDIL, RASHA SHAMSEH Department of Chemistry, Faculty of Science, University of Aleppo, Syria Email: dramadan@scs-net.org Received: 26 Apr 2016 Revised and Accepted: 20 June 2016 ABSTRACT Objective: A simple, direct and accurate spectrophotometric method has been developed for the determination of cefpodoxime proxetil (CEFP) in pure and pharmaceutical formulations by complex formation with bromothymol blue (BTB). Methods: The method involves the formation of yellow ion-pair complexes between BTB reagent and CEFP in chloroform. The two formed complexes ([CEFP]: [BTB] and [CEFP]: [BTB]2) have maximum absorption at λmax 422 nm. The proposed method was validated for specificity, linearity, precision and accuracy, repeatability, sensitivity (LOD and LOQ) and robustness with an average recovery of 99.0-101.4%. Results: The formed complex ([CEFP]: [BTB]2) was measured against the reagent blank prepared in the same manner. Variables were studied in order to optimize the reaction conditions. Molar absorptivity (ε) for two complexes were 8100 and 12600 L. mol -1 . cm -1 , respectively. Beer’s law was obeyed in the concentration range of 0.5576-55.760 μg/ml in the present of 1x10 -3 mol/l of BTB with good correlation coefficient (R 2 = 0.9995). The relative standard deviation did not exceed 4.7%. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.088 and 0.27 μg/ml, respectively. Conclusion: The developed method is applicable for the determination of CEFP in pure and different dosage forms with the average assay of marketed formulations 99.5 to 103.2%, and the results are in good agreement with those obtained by the RP-HPLC reference method. Keywords: Direct spectrophotometric method; Cefpodoxime proxetil; Bromothymol blue; Ion-pair complex. © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Cefpodoxime Proxetil (CEFP) is a third generation cephalosporin antibiotic indicated for the treatment of patients infected with susceptible strains of microorganisms which include a wide range of gram-positive and gram-negative bacteria. It is commonly used to treat acute otitis media, pharyngitis, and sinusitis. It is chemically described as (RS)-1(isopropoxycarbonyloxy) ethyl (+)-(6R, 7R)-7- [2-(2-amino-4-thiazolyl)-2-[(Z) methoxyimino] acetamido]-3- methoxy methyl- 8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2- carboxylate. The molecular formula of cefpodoxime proxetil is C21H27N5O9S2 and the molecular weight is 557.6 g/mol. It is freely soluble in dehydrated alcohol, acetonitrile, methanol and very slightly soluble in water [1-3], see Scheme 1. Bromothymol blue C27H28Br2O5S (BTB), acts as a weak acid in solution. It can thus be in protonated or deprotonated form, appearing yellow or blue, respectively. It is bluish green in neutral solution. The deprotonating of the neutral form results in a highly conjugated structure, accounting for the difference in color. An intermediate of the deprotonating mechanism is responsible for the greenish color in neutral solution, mol. mass 624.38 g [4], see scheme 2. Bromothymol blue has been used as a reagent to form ion pair complexes with drugs as diltiazem HCl [5]. Scheme 1: Chemical structure of cefpodoxime proxetil (CEFP) Scheme 2: Chemical structure of bromothymol blue (C27H28Br2O5S) A simple, sensitive, accurate and rapid UV-Vis spectrophotometric methods have been developed for the estimation of cefpodoxime proxetil in bulk drug and in pharmaceutical dosage form, which shows maximum absorbance at 415 and 425 nm for ion-pair complexes between cefpodoxime proxetil with bromocresol purple and bromocresol green, receptively, in acidic medium and the subsequent extraction of the ion-pair in chloroform [6]. Various spectrophotometric methods [6-24] have been reported for the determination of cefpodoxime proxetil in pure as well as in dosage forms. Most spectrophotometric methods employ extraction procedures. In this case, the extracted complexes were into an organic solvent, which is immiscible with water, and the concentration of the resulting complex in the organic phase is determined spectrophotometrically. The complex extraction technique has some difficulties and inaccuracies due to incomplete extraction or the formation of emulsions between the hydrocarbon solvent and the basic compound-containing solution. In response to the problems resulting from the extraction of the complex, it is better to determine formed complex without extraction [25]. Also, none of the methods reported in the literature is based on the formation of a complex between BTB and CEFP. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 8, 2016