Identification, isolation, and structure elucidation of novel forced degradation products of alectinib hydrochloride

Abstract

AbstractThe present study focuses on novel degradation products of alectinib hydrochloride generated from forced degradation study. In this process, an analytical method was developed that is not only compatible with liquid chromatography–mass spectrometry but sufficiently efficient to capture each of the possible degradation products’ peaks with effective separation from alectinib peak. Alectinib hydrochloride was exposed to acidic, alkali, oxidation, photolytic, and thermal conditions as recommended by the International Conference on Harmonization guidelines. No major degradation was observed under acidic, alkali, photolytic and thermal conditions however the drug was observed to be significantly degraded under oxidative stress conditions generating four novel degradation products that are not reported in the literature. The degradation products were isolated using preparative high‐performance liquid chromatography and then structurally elucidated by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and liquid chromatography–mass spectrometry studies. Most importantly, three degradation products were identified as constitutional isomers. The probable degradation products were identified as N‐oxide impurity, epoxide impurity, N‐hydroxy impurity, and amide impurity, respectively. Moreover, pathway of formation of these degradation products was also postulated in detail.