ABSTRACT Edaravone, a potent free radical scavenger widely employed in the management of acute ischemic stroke and amyotrophic lateral sclerosis, is known to be vulnerable to oxidative degradation, which may compromise its therapeutic efficacy. In this study, the stability of Edaravone was systematically evaluated under diverse stress conditions, including acidic, alkaline, oxidative, thermal, humidity, and photolytic environments, following ICH guidelines. HPLC analysis demonstrated that the drug remained stable under most conditions, but exhibited pronounced degradation when exposed to oxidative stress, resulting in the formation of three distinct impurities. Among these, a major degradation product accounted for approximately 13.8% of the total degradation, while two minor products contributed around 0.8% and 0.2%, respectively. Preparative chromatography enabled the successful isolation of two degradation products, which were structurally characterized using LC‐MS and NMR spectroscopy. The third minor product, due to its low abundance, could not be isolated; however, its structure was tentatively proposed based on mass spectrometric data. Integrating these findings, a plausible oxidative degradation pathway for edaravone was established. The isolated impurities were classified as Class 5 under ICH M7 guidelines, with their non‐mutagenic nature confirmed through validated in silico assessment tools. This comprehensive investigation provides valuable insights into the drug's stability profile and degradation mechanisms, thereby supporting the development of robust pharmaceutical formulations and ensuring long‐term safety and efficacy.
Vallamkonda et al. (Mon,) studied this question.