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

ABSTRACT

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.