STEREOSELECTIVE MICROSOMAL N-OXIDATION OF N-ETHYL-N-METHYLANILINE

The stereoselectivity of metabolic N-oxidation of N-ethyl-N-methylanil ine (EMA) was investigated in vitro following incubation of the compou nd (1mM) with fortified hepatic microsomal preparations of both male W istar rats and New Zealand White (NZW) rabbits. The major metabolites in both species were found to be N-ethylaniline, N-methylaniline and E MA N-oxide. Chromatographic resolution of the N-oxide enantiomers was achieved using a Chiralcel OD stationary-phase with a mobile-phase of hexane : ethanol (98 : 2, v/v). Examination of the enantiomeric compos ition of the N-oxide metabolites indicated a predominance of the (-)-( S)-N-oxide from both species with enantiomeric excesses of 52 +/- 2.5 % and 65 +/- 2.1 % (n=3) in rat and rabbit tissue respectively. These preliminary observations indicate that the N-oxidation of EMA shows pr oduct stereoselectivity, the extent of which varies between species.