Identification of the biliary metabolites of (±)-3-dimethylamino-1,1-diphenylbutane HC1 (recipavrin) in rats

Abstract

1. The in vivo biliary metabolites of (±)-3-dimethylamino-1, 1-diphenylbutane hydrochloride (recipavrin) isolated from Wistar rats have been characterized by g.l.c.-mass spectrometry. 2. Non-conjugated metabolites include recipavrin (1), norrecipavrin (2), diphenylbutanone (3), diphenylbutanone oxime (4), diphenylbutanone phenol (12), diphenylbutanone oxime phenol (14), recipavrin phenol (19), diphenyibutanone O-methylcatechol (16) and diphenylbutanone oxime O-methylcatechol (18). 3. Following β-glucuronidase hydrolysis and extraction from pH10 solution, diphenylbutanone (3), diphenylbutanone oxime (4), an unidentified compound (6), primary amine (8), norrecipavrin (2), recipavrin (1), phenols (12, 14, 15), norrecipavrin phenol (13), O-methylcatechols (16, 18), diphenylbutanol O-methylcatechol (17), recipavrin O-methylcatechol (19) and a secondary formamide (5) were identified by g.l.c.-mass spectrometry. 4. Various extraction solvents were employed in sample workup. The formamide (5) was present regardless of solvent used, while the trace presence of secondary acetamide (7) may be associated with the use of ethyl acetate. 5. Metabolites isolated after β-glucuronidase hydrolysis were characterized by g.l.c.-mass spectrometry of the underivatized form, and as the trimethylsilyl (TMS) derivatives, or following methylation with diazomethane or trimethylanilinium hydroxide (TMAH).