Chemical and electrochemical oxidation of 7-hydroxychlorpromazine

The oxidation of 7-hydroxychlorpromazine, a process associated with several side effects of chlorpromazine therapy, was examined in vitro by electrochemistry and rapid-scanning spectrophotometry. At pH 2, the oxidation results in a quantitative yield of 7,8-dioxochlorpromazine, but several intermediates are observable during the course of the reaction. These include a quinone imine with a half-life of 0.1 s, a monosubstituted benzoquinone with a half-life of approximately 50 s, and a disubstituted benzoquinone with a half-life of approximately 5 min. The concentrations of each intermediate were determined quantitatively as a function of time, and a complete oxidation mechanism is proposed. At pH 7, the yield of 7,8-dioxochlorpromazine is less than at pH 2, and an additional reaction pathway involving direct hydroxylation of the quinone imine is observed. The relationship of these reactions to the pharmacology of the hydroxylated chlorpromazine metabolites is discussed.