High‐Performance Liquid Chromatographic Determination of Ceftibuten and its Metabolite in Biological Fluids: Applications in Pharmacokinetic Studies

Abstract

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