An anticancer drug apalutamide approved by United States Food and Drug Administration in 2018 is one of the most commonly prescribed chemotherapeutic agents used for the treatment of prostate cancer. The present study aims at establishing the chemical structures of all the degradation products of the active pharmaceutical ingredient (API) formed under different forced degradation conditions. Apalutamide degradation was studied under International Council for Harmonisation recommended conditions of hydrolysis (acidic, alkaline, and neutral), oxidation, photolysis, and thermal stress. In total, seven degradation products (DP-1 to DP-7) were observed which were successfully separated on high-performance liquid chromatography and further characterized using liquid chromatography–mass spectrometry quadrupole time-of-flight (LC–MS/MS-QTOF). Degradation pathways for each of the observed DPs have been proposed based on the mass fragmentation pattern of API as well as DPs, identifying the underlying chemical transformations. Prediction of DPs was performed with Zeneth software tool, and the results were compared with the experimental observations. In silico toxicity assessment carried out using Derek suite reveals toxic nature of some of these DPs.

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