Development and validation of a stability-indicating RP-HPLC method for the determination of febuxostat (a Xanthine Oxidase Inhibitor)

Abstract

Febuxostat is a selective inhibitor of xanthine oxidase that is used for the treatment of hyperuricaemia in patients with gout. An isocratic liquid chromatographic method was developed and validated for the determination of febuxostat. Chromatographic separation was achieved on a C18 column using sodium acetate buffer (pH 4.0)- acetonitrile (40:60, v/v), with a flow rate 1.2 mL/min (ultraviolet detection at 254 nm). Linearity was observed in the concentration range of 0.1-200 mg/mL (R2 = 0.9999) with a linear regression equation of y 5 21148x - 2025.1. The limit of quantification was found to be 0.0783 μg/mL and the limit of detection was found to be 0.0257 mg/mL. Febuxostat was subjected to stress conditions of degradation in aqueous solutions, including acidic, alkaline, oxidation, photolysis and thermal degradation. The forced degradation studies were performed by using sodium hydroxide, hydrochloric acid, hydrogen peroxide and thermal and ultraviolet radiation. Febuxostat is more sensitive toward acidic conditions than oxidation and very resistant toward alkaline, thermal and photolytic degradations. The method was validated as per the guidelines of the International Conference on Harmonization. The intra-day and interday precision (relative standard deviation) was found to be 0.29- 0.41 and 0.63-0.76, respectively. The method is simple, specific, precise, robust and accurate for the determination of febuxostat in pharmaceutical dosage forms (tablets). © The Author [2012]. Published by Oxford University Press. All rights reserved.