Isolation and Identification of the New Metabolites of l-[Bis(4-fIuorophenyl)-methyl]-4-(2,3,4-trimethoxybenzyl)piperazine Dihydrochloride (KB-2796) from Rat Bile, Urine and Feces

Abstract

The metabolites of l-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796) in the bile, urine and feces in rats were investigated after oral administration of [methine-14C], [benzyl-14C] and unlabelled KB-2796. Their structures were characterized by thin-layer chromatography, mass spectrometry, proton nuclear magnetic resonance and comparison with synthesized authentic compounds. The main pathways of biotransformation of KB-2796 in rats were: (a) O-demethylation at each methoxy group of the trimethoxybenzyl moiety, (b) N-dealkylation at 1 and 4-position of the piperazine ring and (c) hydroxylation at 5-position of the 2,3,4-trimethoxyphenyl ring. © 1991, The Pharmaceutical Society of Japan. All rights reserved.