HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF CEFTIBUTEN AND ITS METABOLITE IN BIOLOGICAL-FLUIDS - APPLICATIONS IN PHARMACOKINETIC STUDIES

An HPLC method with UV detection was developed for the analysis of ceftibuten (cis-isomer) and its metabolite (trans-isomer of ceftibuten) in plasma and urine. The detection was performed at 254 nm. The procedure for the plasma assay involves the addition of an internal standard (ceftazidime), followed by treatment of the samples with acetonitrile and dichloromethane. The urine samples, after dilution (10- to 40-fold), were analyzed by a column-switching technique without internal standard. The proposed technique is reproducible, selective, reliable, and sensitive. Linear detector responses were observed for the calibration curve standards in the ceftibuten concentration range of 0.10 to 20 mg/L for plasma and 0.10 to 50 mg/L for urine, and in the metabolite concentration range of 0.20 to 4 mg/L for plasma and 0.20 to 16 mg/L for urine. The limit of quantitation is 0.1 mg/L for ceftibuten and 0.2 mg/L for the transisomer in plasma and urine. The reproducibility of the analytical method according to the statistical coefficients is similar to 7%. The accuracy of the method is good; that is, the relative error is <5%. The methods were applied to pharmacokinetic studies of ceftibuten after multiple oral administration (400 mg every 12 h for 8 days) to healthy volunteers.