Isolation and identification of forced degradation products of Febuxostat

Abstract

The current study explains the degradation behavior of Febuxostat API, a non‐purine xanthine oxidase inhibitor used to treat hyperuricemia. A degradation study was carried out as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, and the study confirms that the Febuxostat is largely stable in thermal, photolytic, oxidative, and basic hydrolytic conditions and labile in acid hydrolysis conditions. There were four different degradation products (DPs) found during acid hydrolysis; of these, DPs 2, 3, and 4 are new and have never been reported before, while DP 1 is known and has already been published. All these DPs were identified using ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC‐MS) analysis, purified by using preparative HPLC, and characterized using high‐resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy techniques. The formed DPs are by the hydrolysis of the cyano functional group of Febuxostat and the esterification of DP‐1 under acidic conditions. All DP's structural characterization was carried out using NMR spectroscopy and HRMS. The present study describes concrete confirmation of DP structures and it explains the stability behavior of the Febuxostat. The current method is also used to identify DPs with shorter runtime in the future.