PROPERTIES OF MELARSAMINE HYDROCHLORIDE (CYMELARSAN) IN AQUEOUS-SOLUTION

The antitrypanosomal drug melarsamine hydrochloride (MelCy) (trade nam e, CSmelarsan) is a melamino-phenylarsine made by conjugation of one e quivalent of melarsen oxide and two equivalents of cysteamine. Immedia tely after it was dissolved in water, the compound was found to exist as an equilibrium mixture containing MelCy (33%), MelCy which had lost one cysteamine moiety (MelCy -1; 24%), melarsen oxide (33%), and free cysteamine. Small amounts (<1%) of the oxidation products derived fro m the last two components were also formed (cystamine and sodium melar sen). On incubation at room temperature, the MelCy content decreased s teadily, with an associated increase in the melarsen oxide and sodium melarsen contents. After 5 days in solution at room temperature, 27% o f the arsenical agent was R MelCy, 14% was MelCy -1, 42% was melarsen oxide, and 17% was sodium melarsen. Since H2O2 production was detectab le in MelCy or cysteamine solutions and the addition of small amounts of exogenous H2O2 readily converted the trivalent melarsen oxide to th e pentavalent sodium melarsen, it is hypothesized that the nonenzymati c conversion of cysteamine to cystamine produced H2O2, which then oxid ized melarsen oxide to sodium melarsen. Similar time course experiment s showed that melarsonyl potassium and melarsoprol were more stable in solution.