Voltammetric determination of cefixime in pharmaceuticals and biological fluids Rajeev Jain a , Vinod K. Gupta b,c,⇑ , N. Jadon a , K. Radhapyari a a School of Studies in Chemistry, Jiwaji University, Gwalior 474011, India b Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, India c Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia article info Article history: Received 20 May 2010 Received in revised form 14 July 2010 Accepted 24 July 2010 Available online 1 August 2010 Keywords: Square-wave stripping voltammetry Differential pulse stripping voltammetry Pharmaceuticals Biological fluid Cefixime abstract Electroreduction and adsorption of cefixime was studied in phosphate buffer by cyclic voltammetry (CV), differential pulse cathodic adsorptive stripping voltammetry (DPCAdSV), and square-wave cathodic adsorptive stripping voltammetry (SWCAdSV) at hanging mercury drop electrode (HMDE). These fully val- idated sensitive and reproducible cathodic adsorptive stripping voltammetric procedures were applied for the trace determination of the bulk drug in pharmaceutical formulations and in human urine. The optimal experimental parameters were as follows: accumulation potential = 0.1 V (vs. Ag/AgCl, 3 M KCl), accumu- lation time = 50 s, frequency = 140 Hz, pulse amplitude = 0.07 V, and scan increment = 10 mV in phosphate buffer (pH 2.6). The first peak current showed a linear dependence with the drug concentration over the range of 50 ng ml 1 to 25.6 lg ml 1 . The achieved limit of detection and limit of quantitation were 3.99 and 13.3 ng ml 1 by SWCAdSV and 7.98 and 26.6 ng ml 1 by DPCAdSV, respectively. The procedure was applied to assay the drug in tablets. Applicability was also tested in urine samples. Peak current was linear with the drug concentration in the range of 1 to 60 lg ml 1 of the urine, and minimum detectability was found to be 12.6 ng ml 1 by SWCAdSV and 58.4 ng ml 1 by DPCAdSV. Ó 2010 Elsevier Inc. All rights reserved. Cefixime is a broad-spectrum oral cephalosporin that was ap- proved by the U.S. Food and Drug Administration in 1997 for the treatment of mild to moderate bacterial infections. It is effective against a wide variety of bacteria organisms such as Staphylococcus pneumoniae, Haemophilus influenzae, Escherichia coli, Neisseria gonor- rhoeae, and Streptococcus pyogenes (group A b-hemolytic strepto- cocci) [1–4]. Cefixime is effective against susceptible bacteria causing infection of the middle ear, tonsillitis, throat infections, lar- yngitis, bronchitis, urinary tract infections (UTIs), 1 gonorrhea, and pneumonia [5–8]. Cefixime is a primary candidate for switch therapy owing to its very good efficacy and safety profile [9]. It is found to be safe, effective, and an inexpensive oral option for the treatment of multidrug-resistant enteric fever and pharyngitis in children [10–12]. Chemically, cefixime (Scheme 1) is [6R-[6a,7b(Z)]]-7-[[(2- amino-4-thiazoyl)[(carboxymethoxy)imino]acetyl]amino]-3-ethenyl- 8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ne-2-carboxylic acid [13]. For clinical investigations such as pharmacokinetic studies, development of sensitive and selective analytical methods for the determination of drugs in biological fluids is required. A thorough literature search revealed that several analytical methods have been used, including derivative spectrophotometric [14] and chro- matographic [15,16] techniques for the determination of cephalo- sporins in dosage form and body fluids, but there are only few analytical methods for the determination of cefixime in pharma- ceutical preparations and biological fluids. High-performance li- quid chromatography (HPLC) is a widely reported technique and has been applied for the determination of cefixime in human urine, plasma, cerebrospinal fluid, bulk, and pharmaceuticals [17,18]. In addition, various spectrophotometry [19], high-performance capil- lary electrophoresis [20], and high-performance thin-layer chro- matography (TLC) [21] techniques have also been applied for the determination of cefixime and its metabolites in drug formula- tions. Recently, a sensitive liquid chromatography (LC)–tandem mass spectrometric method has been developed for the assay of cefixime in human plasma, and the lower limit of quantification was found to be 0.05 lg ml 1 [22]. Cefixime has been the subject of a monograph in the U.S. Pharmacopeia [23]. Although the selectivity and limit of detection (LOD) have been improved in most of the reported methods, they are time-consum- ing, they involve a large number of complicated pretreatment steps for analysis, and they require sophisticated and expensive instrumentation. During recent decades, modern voltammetric 0003-2697/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.ab.2010.07.027 ⇑ Corresponding author at: Department of Chemistry, Indian Institute of Tech- nology Roorkee, Roorkee 247667, India. Fax: +91 1332 273560. E-mail addresses: vinodfcy@gmail.com, vinodfcy@iitr.ernet.in (V.K. Gupta). 1 Abbreviations used: UTI, urinary tract infection; HPLC, high-performance liquid chromatography; TLC, thin-layer chromatography; LC, liquid chromatography; LOD, limit of detection; SWCAdSV, square-wave cathodic adsorptive stripping voltamme- try; DPCAdSV, differential pulse cathodic adsorptive stripping voltammetry; HMDE, hanging mercury drop electrode; CV, cyclic voltammetry; BR, Britton–Robinson; RSD, relative standard deviation; CV, coefficient of variation; LOQ, limit of quantitation; LLOQ, lower limit of quantitation; Cpe, controlled potential electrolysis. Analytical Biochemistry 407 (2010) 79–88 Contents lists available at ScienceDirect Analytical Biochemistry journal homepage: www.elsevier.com/locate/yabio