Coutts R T, Su P, Baker G B, Daneshtalab M
Neurochemical Research Unit, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
J Chromatogr. 1993 Jun 2;615(2):265-72. doi: 10.1016/0378-4347(93)80340-a.
A metabolism study of imipramine (IMI) has been conducted in vitro with commercially available human CYP2D6 isozyme expressed in a human AHH-1 TK +/- cell line. This enzyme system catalyzed the anticipated ring-oxidative biotransformation of IMI to 2-hydroxyimipramine (2-OH-IMI). In addition, however, the human CYP2D6 isozyme preparation was found to be unequivocally involved in the N-dealkylation of IMI to desmethylimipramine (DMI). 2-Hydroxydesipramine was also identified as a trace metabolite of IMI, but no 10-hydroxyimipramine was detected. The 2-OH-IMI metabolite was unstable and disappeared from metabolic solutions on standing. A procedure involving the O-acetylation of 2-OH-IMI was developed to minimize this decomposition. When an authentic sample of 10-OH-IMI was subjected to the same acetylation procedure, it was partially dehydrated to 10,11-dehydroimipramine, but also underwent unexpected degradations to two other products in which the dimethylaminopropyl side-chain was deaminated. Plausible structures for these two decomposition products are suggested from their gas chromatographic-mass spectrometric behaviour.
