Metabolic fate of the antipsychotic agent, mazapertine, in man--API-MS and MS/MS identification of urinary metabolites.
The in vivo metabolism of the antipsychotic agent mazapertine was studied after oral administration of mazapertine succinate (40 mg/subject) to two healthy volunteers, and urine (0-24 hours) was obtained for metabolite identification using API-ionspray LC/MS and MS/MS analysis. Unchanged mazapertine (12% of the sample) plus 10 metabolites were profiled, quantified, and tentatively identified on the basis of MS data, Glusulase-hydrolysis, and by comparison to synthetic samples. The formation of mazapertine metabolites are via seven metabolic pathways: (1) phenylhydroxylation, (2) piperidyl oxidation, (3) O-dealkylation, (4) N-dephenylation, (5) oxidative N-debenzylation, (6). depiperidylation, and (7) glucuronidation. Pathways 1, 2, 5 and 7 formed 4-OH-phenyl-mazapertine (M1, 18%) and 4-OH-piperidyl (M2, 14%)-mazapertine, carboxybenzoylpiperidine (M8, 10%) and its glucuronide (M9, 14%) as four major metabolites. Six moderate and minor metabolites (M3-M7 & M10; each < or =10%) formed via a combination of pathways 1-6. Mazapertine is extensively metabolized in humans.
Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring House, PA 19477, USA.
Wu-Nan
WN
Wu
Linda A
LA
McKown
Allen B
AB
Reitz
D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine*; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization
D014150:Antipsychotic Agents; D010879:Piperazines; C086897:mazapertine succinate