Kinetics and mechanism of solid state imidapril hydrochloride degradation and its degradation impurities identification

Abstract

A detailed stability testing of solid state imidapril hydrochloride (IMD) was performed and its degradation products were identified. The analysis was conducted according to ICH guidelines Q1A(R2). Pure IMD samples were exposed to stress conditions of elevated temperature and relative humidity (T = 363 K, RH = 76.4%) in order to accelerate degradation. The regular loss of IMD content with time, and the formation of two degradation impurities were observed. The appropriate reaction rate constants k (for IMD degradation and for the formation of product I and II) were calculated using Prout-Tompkins equation. The obtained degradation products were separated and identified by means of LC-MS technique. Based on the obtained m/z values, the masses and the structures of the formed degradation impurities were established. Also IMD degradation scheme was constructed. It was demonstrated that under the applied analytical conditions, IMD degradation follows an autocatalytic reaction model with the rate constant k = (4.764 ± 0.34)×10 ⁻⁶ s ⁻¹ and with the parallel formation of two degradation products: imidaprilat and the diketopiperazine derivative. The obtained experimental results are in agreement with IMD degradation pathways proposed theoretically.