Stereoselective microsomal N-oxidation of N-ethyl- N-methylaniline

The stereoselectivity of metabolic N-oxidation of N-ethyl- N-methylaniline (EMA) was investigated in vitro following incubation of the compound (1mM) with fortified hepatic microsomal preparations of both male Wistar rats and New Zealand White (NZW) rabbits. The major metabolites in both species were found to be N-ethylaniline, N-methylaniline and EMA 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 composition 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 product stereoselectivity, the extent of which varies between species.