Characterization and identification of the metabolites of fenoctimine using in vitro drug metabolizing systems.

Fenoctimine sulphate (4-(diphenylmethyl)-1-[(octylimino)methyl]piperidine sulphate) and one of its metabolites, 1-formyl-4-(diphenylmethyl) piperidine (RWJ-34321), were incubated with a rat liver post-mitochondrial supernatant preparation and an NADPH generating system. The metabolites, 7-hydroxyoctyl fenoctimine and 7-oxoocytl fenoctimine were identified as in vitro oxidative metabolites of fenoctimine on the basis of mass spectrometry and thin layer chromatography in comparison to authentic samples. RWJ-34321, a third metabolite, was confirmed as a hydrolyzed product of fenoctimine on the same basis. In separate incubations with RWJ-34321, one metabolite (4-(diphenylmethyl)piperidine), was identified as an in vitro metabolite of RWJ-34321 by mass spectrometry and thin layer chromatography. Thus, the in vitro metabolism of fenoctimine by rat liver homogenates resulted in the oxidation of the aliphatic chain at the seven carbon, initially to an alcohol and then to a ketone. The metabolism of RWJ-34321 resulted in decarbonylation of the formyl carbon.