Isolation and identification of hydroxylated maprotiline metabolites

Lipophilic maprotiline metabolites were extracted from human urine and animal excreta, with or without prior enzymic hydrolysis, purified by repeated t.l.c. and their structures determined by u.v., n.m.r. and mass spectrometry. Urine from patients under treatment with maprotiline contained the isomeric phenols, 2- and 3-hydroxymaprotiline, the 2,3-dihydrodiol, and an alcoholic metabolite, besides smaller quantities of the corresponding N-demethylated compounds. In dog urine and/or faeces the same products of aromatic hydroxylation were present as in human urine and in addition 3-hydroxy-2-methoxymaprotiline; alcohols were not detected. The only metabolites identified in rabbit urine and rat bile were 3-hydroxy- and 3-hydroxy-2-methoxymaprotiline.