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 simultaneous determination of an active metabolite (FCE22101) and open-ring metabolites (P1, P2) of a penem antibiotic, FCE22891, in dog plasma was developed. Plasma samples were pretreated only by ultrafiltration for the determination of the metabolites. The filtrates were directly analyzed by a reversed-phase high-performance liquid chromatographic system using a two-sided bracketing injection technique. The quantitation limits of FCE22101, P1 and P2 were 0.03, 0.1 and 0.15 microgram ml-1, respectively. Analysis of the spiked plasma samples demonstrated the good accuracy and precision of the method. The proposed method was applied to the pharmacokinetic studies of an active metabolite and open-ring metabolites after oral administration of a penem antibiotic, FCE22891, in dogs. In addition, the plasma levels of unchanged FCE22891 and the possible changes of formaldehyde and acyl-L-carnitine levels in plasma, which will be generated from the ester group of FCE22891, were also investigated.
Matsuoka
M
M
Analytical Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Imado
N
N
Maki
T
T
Banno
K
K
Sato
T
T
D000108:Acetylcarnitine / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002087:Butyrates / Q000097:blood; D015780:Carbapenems / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005557:Formaldehyde / Q000097:blood; D006863:Hydrogen-Ion Concentration; D007769:Lactams; D011355:Prodrugs / Q000032:analysis*; D015203:Reproducibility of Results; D013844:Thiazoles / Q000097:blood
C114282:2-(4-carboxy-5-methylene-2H-thiazol-2-yl)-3-hydroxybutanoic acid; D000900:Anti-Bacterial Agents; D002087:Butyrates; D015780:Carbapenems; D007769:Lactams; D011355:Prodrugs; D013844:Thiazoles; D005557:Formaldehyde; D000108:Acetylcarnitine; C041561:FCE 22891; C040033:ritipenem