Validated HPLC method for the pharmacokinetic study of oral extended-release cefpodoxime proxetil chitosan-alginate...

The aim of this study is to develop a simple and applicable HPLC method for the detection of cefpodoxime acid (CFA) in rabbit plasma after oral administration of cefpodoxime proxetil (CFP) loaded chitosan-alginate (CH-ALG) beads formulation. CFP is a prodrug that is deesterified in vivo to its active metabolite CFA to exhibit antibiotic activity. Chromatographic separation of CFA and internal standard (IS) was achieved by a RP18(C18), Phenomenax®100, (250×4.6mm) with the mobile phase consisting of (0.02mol/l (20mM) ammonium acetate solution and acetonitrile (92:8, v/v, pH=4.6) at a flow rate of 1.0ml/min. The method was validated according to the requirements of US-FDA guidelines for bioanalytical method validation. The linear regression analysis for the calibration plots showed good linear relationship (R²=0.9905) in the working concentration range of 0.5-50μg/ml. The limits of detection and quantification (S/N=3) were 0.069 and 0.136μg/ml. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The analyte was found to be stable after a number of stability studies. The proposed HPLC method was successfully applied to pharmacokinetic study in rabbits for CFP loaded CH-ALG beads and marketed immediate release (IR) tablets. All pharmacokinetic parameters were assessed.