Hepatic metabolism of the new antipsychotic agent, mazapertine, in rat--API-MS/MS identification of metabolites.
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.
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Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring House, PA 19477, USA.
McKown
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Reitz
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D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D008745:Methylation; D010879:Piperazines / Q000493:pharmacokinetics*; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D014150:Antipsychotic Agents; D010879:Piperazines; C086897:mazapertine succinate