The present study focuses on novel degradation products of nelarabine generated from forced degradation study. In the process, a novel analytical method was developed which was not only compatible with liquid chromatography‐mass spectrometry but also had the efficiency to capture each of the possible degradation products with sufficient separation from the nelarabine peak. Nelarabine was exposed to acidic, alkali, oxidation, photolytic, and thermal stress conditions as recommended by International Conference on Harmonization guidelines. No major degradation was observed under photolytic and thermal conditions however the drug was observed to be significantly degraded under acidic, alkali, and oxidative stress conditions generating a total of nine novel degradation products which are hitherto not been reported in the literature. The major degradation products obtained under acidic and alkali conditions were isolated using preparative high‐performance liquid chromatography and their structure was elucidated using nuclear magnetic resonance spectroscopy and high‐resolution mass spectroscopic studies. Moreover, probable pathways for the formation of these degradation products were also outlined.

The 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.