Simultaneous determination of a new inhibitor of acyl CoA:cholesterol acyltransferase, YM17E, and five metabolites using high-performance liquid chromatography with electrochemical detection.
We describe a reversed-phase high-performance liquid chromatographic method for the determination in plasma of YM17E (I), an inhibitor of acyl CoA:cholesterol acyltransferase, and its five metabolites using electrochemical detection. This method enables simultaneous quantification of I and five active metabolites. The plasma sample is extracted by a one-step solid-phase extraction using a SepPak C18 cartridge, with high recovery and reproducibility of the analytes. The method is sensitive and the limits of determination are 0.5 ng/ml for I and 1 ng/ml for metabolites M1, M2-a, M2-b, M3 and M4. This method is applicable to rat, dog and human plasma, and is useful for pharmacokinetic studies.
Uchida
T
T
Drug Metabolism Department, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Usui
T
T
Watanabe
T
T
Higuchi
S
S
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D004563:Electrochemistry; D006801:Humans; D008297:Male; D010671:Phenylurea Compounds / Q000097:blood* / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D010671:Phenylurea Compounds; C080390:YM17E; D002785:Sterol O-Acyltransferase