SIMULTANEOUS DETERMINATION OF AN ACTIVE METABOLITE AND OPEN-RING METABOLITES BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AND PHARMACOKINETIC STUDIES OF A PENEM ANTIBIOTIC, FCE22891, IN DOGS

A sensitive high performance liquid chromatographic method for the sim ultaneous determination of an active metabolite (FCE22101) and open-ri ng metabolites (P1, P2) of a penem antibiotic, FCE22891. in dog plasma was developed. Plasma samples were pretreated only by ultrafiltration for the determination oi.;he metabolites. The filtrates were directly analyzed by a reversed-phase high-performance liquid chromatographic system using a two-sided bracketing injection technique. The quantitat ion limits of FCE22101, Pt and P2 were 0.03, 0.1 and 0.15 mu g ml(-1), respectively. Analysis of the spiked plasma samples demonstrated the good accuracy and precision of the method. The proposed method was app lied to the pharmacokinetic studies of an active metabolite and open-r ing metabolites after oral administration of a penem antibiotic, FCE22 891, in dogs. In addition, the plasma levels of unchanged FCE22891 and the possible changes of formaldehyde and acyl-L-carnitine levels in p lasma, which will be generated from the ester group of FCE22891, were also investigated. (C) 1998 Elsevier Science B.V. All rights reserved.