Simple high-performance liquid chromatographic method for the separation of 3,6-diacetylmorphine hydrochloride (heroin) and hydrolysis products.

The application of reversed-phase high-performance liquid chromatography to the measurement of 3,6-diacetylmorphine (DAM) hydrochloride and its degradation products is described. This method has been applied to study the kinetics of the DAM hydrolysis at 26 +/- 0.1 degrees and 48 +/- 0.1 degrees. The hydrolysis of DAM involved a two-step first-order sequential mechanism between pH 3 and 8.6. The first-order rate constants of each step at all pH levels have been determined. The pH rate profile was constructed from kinetic measurements and demonstrated that stability of DAM hydrochloride solutions was optimal at pH 4.3. This information is being applied to the development of parenteral dosage forms of DAM hydrochloride.