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 cef tibuten (cis-isomer) and its metabolite (trans-isomer of ceftibuten) i n plasma and urine. The detection was performed at 254 nm. The procedu re 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 stan dard. The proposed technique is reproducible, selective, reliable, and sensitive. Linear detector responses were observed for the calibratio n 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 c oncentration range of 0.20 to 4 mg/L for plasma and 0.20 to 16 mg/L fo r 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 t he analytical method according to the statistical coefficients is simi lar to 7%. The accuracy of the method is good; that is, the relative e rror is <5%. The methods were applied to pharmacokinetic studies of ce ftibuten after multiple oral administration (400 mg every 12 h for 8 d ays) to healthy volunteers.