HPLC assay method for ceftibuten in plasma and its application to pharmacokinetic study

The purpose of this study was to validate a reliable analytical method for pharmacokinetic study of ceftibuten in human plasma by high performance liquid chromatography (HPLC) system with UV detection. Ceftizoxime was used as the internal standard. After plasma sample was precipitated with acetonitrile and dichloromethane, the supernatant was directly injected into the HPLC system. Separation was performed on a Capcell Pak C₁₈ UG120 column (4.6 mm × 250 mm, 5 μm particles) with a mobile phase of acetonitrile/50 mM ammonium acetate (5: 95, v/v) and UV detection at a wavelength of 262 nm. The intra- and inter-day precision expressed as the relative standard deviation was less than 15%. The lower limit of quantification was 0.5 hg/mL of ceftibuten using 0.5 mL of plasma. The calibration curve was linear in concentration range of 0.5-30 μg/mL (r ² = 0.9998). The mean accuracy was 96-102%. The coefficient of variation (precision) in the intra- and inter-day validation was 0.9-3.9 and 0.9-2.4%, respectively. The pharmacokinetics of ceftibuten was evaluated after a single oral administration of 400 mg to healthy volunteers. The AUC_{0-9 h}, c _max, T _max, and T _1/2 were 86.6 ± 12.7 μg h/mL, 18.4 ± 1.5 μg/mL, 2.63 ± 0.83 and 2.65 ± 0.41 h, respectively. The method was demonstrated to be highly reproducible and feasible for pharmacokinetic studies of ceftibuten in eight volunteers after oral administration (400 mg as ceftibuten).