Stability of Brompton mixtures: determination of heroin (diacetylmorphine) and cocaine in presence of their hydrolysis products.

The application of a rapid, selective, and sensitive reversed-phase high-performance liquid chromatographic method to the separation of the hydrochloride salts of heroin (diacetylmorphine) and cocaine and their hydrolysis products is described. The method was used to study the stability of heroin and cocaine in Brompton mixtures in pharmaceutically useful pH range and vehicles at different temperatures. The pH range of optimal stability for both heroin and cocaine was 3.0-3.5. The disappearance of heroin and cocaine in Brompton mixtures followed pseudo-first-order kinetics in buffered solutions. Increased alcohol and decreased syrup concentrations diminished heroin hydrolysis but did not influence cocaine stability. Substitution of morphine for heroin in Brompton mixtures markedly increased the rate of cocaine hydrolysis.