Abstract
1. Incubation of N, N-dimethylaniline (DMA) with isolated rat hepatocytes resulted in the production of N-methylaniline, aniline, N, N-dimethylaniline N-oxide (DMA N-Oxide) and a highly water-soluble metabolic tentatively identified as N-methylaniline N-glucuronide.
2. After the removal of aniline, N-methylaniline and DMA, treatment of the media with either strong acid or β-glucuronidase, resulted in the release of N-methylaniline, identified by chromatography and mass spectrometry.
3. Pre-incubation of rat hepatocytes with 2 mM D-galactosamine, which decreased 7-hydroxycoumarin conjugate formation by 40%, selectively decreased the formation of this highly water-soluble metabolite from DMA by 70%. DMA N-demethylase and N-oxidase activities remained unchanged.
4. Incubation of rat hepatocytes with N-methylaniline resulted in the production of the novel metabolite, the formation of which was proportional to cell number, incubation time, and N-methylaniline (substrate) concentration.
5. The N-glucuronidation of the secondary N-alkylarylamine, N-methylaniline, by rat hepatocytes represents a quantitatively important and previously uncharacterized route of metabolism in these cells. Further studies are, however, required to identify this metabolite unequivocally as the N-glucuronide of N-methylaniline.