In vivo phenolic metabolites of N-alkylamphetamines in the rat. Evidence in favor of catechol formation.

The major in vivo metabolites of 1-phenyl-2-(n-propylamino)propane (N-n-propylamphetamine) in the rat were phenolic compounds, identified as 1-(4-hydroxyphenyl)-2-(n-propylamino)-propane (metabolite A) and 1-(4-hydroxy-3-methoxyphenyl)-2-(n-propylamino)propane (metabolite B) by gas chromatography-mass spectrometry, and by comparison with authentic synthetic samples of A and B. Metabolites A and B were formed from the substrate in 18.3% and 3.3% yields, respectively, and are excreted in the urine mainly in conjugated form. In vivo metabolism in the rat of the homolog, 1-phenyl-2-(n-butylamino)propane (N-n-butylamphetamine) resulted in the formation of two homologous metabolites in similar yields, which were tentatively identified, from their gas chromatographic and mass spectrometric behav-propane (metabolite A) and 1-(4-hydroxy-3-methoxyphenyl)-2-(n-propylamino)propane (metaboior and by comparison with metabolites A and B, as 2-(n-butylamino)-1-(4-hydroxyphenyl)propane (metabolite C) and 2-(n-butylamino)-1-(4-hydroxy-3-methoxyphenyl)propane (metabolite D). It is suggested that the methylated metabolites B and D were formed from metabolites A and C, respectively, via catecholamine intermediates.