Hepatic metabolism of the new antipsychotic agent, mazapertine, in rat - API-MS/MS identification of metabolites

被引：5

作者：

Wu, WN ^{[1
]}

McKown, LA ^{[1
]}

Reitz, AB ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, LLC, Spring House, PA 19477 USA

来源：

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS | 2003年 / 28卷 / 04期

关键词：

mazapertine; antipsychotic agent; rat hepatic S9; in vitro metabolism; ms/ms;

D O I：

10.1007/BF03220180

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The In vitro biotransformation of the antipsychotic agent, mazapertine was studied after incubation with rat hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged mazapertine (42% of the sample) plus 12 metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS data. The proposed metabolic pathways for mazapertine are proposed, and the 6 metabolic pathways are: (1) phenylhydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, and (6) dehydration. Pathways 1 to 3 formed 4-OH-phenyl (M1, 10%) and 4-OH-piperidyl (M2, 9%)-mazapertine, O-desisopropyl mazapertine (M3, 17%), and N-desbenzoylpiperidine-mazapertine (M8, 14%) as 4 major metabolites. Mazapertine is extensively metabolized in rat hepatic S9 fraction.

引用

页码：279 / 286

页数：8