Identification of a dithiol intermediate metabolite of malotilate in rats

Abstract

1. A chemically unstable dithiol intermediate metabolite of malotilate was identified by g.l.c.-mass spectrometry after conversion of the dithiol to a stable derivative by a cyclization reaction with 1,3-dichloroacetone. The dithiol, namely, 2,2-di(isopropoxycarbonyl)ethylene-1,1-dithiol, was present in rat liver at low concentrations.

2. A study of glucuronidation in vitro indicated that the dithiol was converted to the corresponding thio-glucuronide by rat hepatic microsomal enzymes.

3. It was thus confirmed that metabolism of malotilate proceeds via the dithiol intermediate to form the thio-glucuronide, which is a major metabolic pathway.