Hydroxyl radical-mediated conversion of morphine to morphinone

Abstract

1. The hydroxyl radical-mediated conversion of morphine to morphinone (MO) was examined as an alternative to the enzymic reaction.

2. Hydroxyl radicals were generated by autoxidation of ascorbate in the presence of iron and EDTA. This system oxidized morphine to MO which was identified by h.p.l.c. and t.l.c. The reaction was dependent on the concentration of added Fe²⁺ and required the addition of ascorbate when Fe³⁺ was used.

3. Catalase inhibited production of MO whereas superoxide dismutase (SOD) had no effect. Addition of a large amount of H₂O₂ to the system resulted in a significant decrease in production of MO. No MO production was initiated by H₂O₂ itself. The oxidation of morphine was inhibited by typical hydroxyl radical-scavenging agents. These results indicate that morphine undergoes oxidation to MO by hydroxyl radical.