Identification of a nitrone as an in vitro metabolite of N-methylamphetamine

The relatively labile nitrone, alpha-methyl-(N-methylene) benzeneethanamine N-oxide was isolated from incubates of (+/-)-N-methylamphetamine with fortified liver honogenates from rats and rabbit. Identification of the nitrone was confirmed directly by gas chromatography and gas chromatography mass spectrometry and, after its conversion to isoxazolidine adducts by the action of methyl and ethyl acrylate. An authentic sample of the nitrone was synthesized unequivocally form N-hydroxyamphetamine and formaldehyde. The isomeric nitrone, N-(alpha-methylbenzeneethylidene) methylamine N-oxide, was also synthesized and its gas chromatographic and gas chromatographic mass spectrometric characteristics determined to confirm that the metabolically formed nitrone was not N-(alpha-methylbenzeneethylidene) methylamine N-oxide. Two previously unreported metabolites of (+/-)-Nmethylamphetamine, N-hydroxyamphetamine and 1-hydroxy-1-phenyl-2-propanone, were isolated from rat in vitro experiments; the latter metabolite was not produced in vitro by rabbit liver homogenates.