Identification and characterization of stress degradation products of febuxostat employing UPLC-UV/PDA and LC-MS/TOF studies

Febuxostat is a xanthine oxidase inhibitor approved by the US FDA for long-term treatment of gout and hyperuricemia. There were no reports on identification and characterization of stress degradation products of the drug.Febuxostat was subjected to forced decomposition conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as per the ICH guideline Q1A(R2). The degradation products were formed were subjected to UPLC on C18 (100 mm x 4.6 mm; 2.6μ, Kinetex) column using isocratic elution method. Detection wavelength was 317 nm. The developed method was extended to UPLC-MS/TOF studies to identify and characterize the degradation products.The drug showed significant degradation under alkaline/neutral hydrolytic, alkaline/acidic photolytic and oxidative conditions, while it remained stable in acid hydrolytic, neutral photolytic and thermal conditions. In total, eight degradation products (I-VIII) were formed, which could be adequately resolved from the drug by the developed UPLC method. Out of the eight degradation products identified from the LC/UV chromatogram, five (III-IV and VI-VIII) could be characterized through their MS/TOF spectral data. The degradation pathway leading to generation of the products was postulated and this is not reported so far.Forced degradation studies were conducted on Febuxostat and the generated degradation products were identified and by their mass spectral data obtained from LC-MS studies.