Gas chromatographic analysis of chlorpromazine and its metabolites formed by hepatic microsomes—I: Influence of magnesium

The metabolism of chlorpromazine has been studied using rat and rabbit liver microsomal preparations and the Curry extraction and gas Chromatographic technique for the compounds involved, namely chlorpromazine, chlorpromazine N-oxide, monodemethyl chlorpromazine, didemethyl chlorpromazine, chlorpromazine sulfoxide and monodemethyl chlorpromazine sulfoxide. In both liver systems, chlorpromazine N-oxide and monodemethyl chlorpromazine were found to be the major metabolites. The former accounted for 38–62 per cent of the chlorpromazine disappearing under various experimental conditions, while the latter amounted to 28–77 per cent in the same experiments. The 92–104 per cent of the CPZ disappearing could be accounted for by the appearance of the metabolites measured. The addition of Mg 2+ to the microsomal drug oxidase experimental suspensions caused an increase in the disappearance of chlorpromazine in both the rat and rabbit. In the rat. Mg 2+ caused little or no increase in chlorpromazine N-oxiae appearance but increased the formation of monodemethyl chlorpromazine by a factor of 2 to 3. In the rabbit the opposite was true.