Identification and characterization of stress degradation products of febuxostat employing ultra-performance liquid chromatography-ultraviolet/photodiode array and liquid chromatography-mass spectrometry/time-of-flight studies.

Abstract

Febuxostat (FEB) is a xanthine oxidase inhibitor approved by the U.S. Food and Drug Administration for long-term treatment of gout and hyperuricemia. There were no reports on identification and characterization of stress degradation products of the drug. FEB was subjected to forced decomposition conditions such as hydrolysis (neutral, acidic, and alkaline), oxidation, photolysis, and thermal stress, per the ICH guideline Q1A(R2). The degradation products formed were subjected to ultra-performance liquid chromatography (UPLC) on a C18 Kinetex column (100 × 4.6mm, 2.6μm) using isocratic elution method. Detection wavelength was 317 nm. The developed method was extended to UPLC-mass spectrometry/time of flight (MS/TOF) studies to identify and characterize the degradation products. The drug exhibited significant degradation under alkaline/neutral hydrolytic, alkaline/acidic photolytic, and oxidative conditions, whereas it remained stable under acid hydrolytic, neutral photolytic, and thermal conditions. In total, eight degradation products (I-VIII) were formed, which could be adequately determined from the drug using the developed UPLC method. Of the eight degradation products identified from the liquid chromatography-ultraviolet (LC-UV) chromatogram, five (III and IV and VI-VIII) could be characterized using their MS/TOF spectral data. The degradation pathway leading to the formation of the products was postulated, and this is not reported so far. Forced degradation studies were conducted on FEB, and the degradation products produced were identified by their mass spectral data obtained using LC-MS studies.