A stability-indicating liquid chromatography - diode array detection method for quantification of febuxostat in pharmaceuticals: a recent application to chemometrics based method development and comparative greenness assessment

Abstract

With an increased demand for anti-gout drugs, the need for a quality-controlled drug product also arises. In this context, a new liquid chromatography method was developed for quantifying febuxostat that integrates chemometrics principles and assesses the method's eco-friendly nature. Systematized risk assessment identified that organic proportion, flow rate, and pH are the critical method variables and were subsequently optimized using a Box-Behnken design. The validation studies were performed using the optimized chromatographic conditions of 80% organic solvent, 1.0 mL/min flow rate, and a pH value of 6.8 on a C-18 column. The analyte eluted at 2.2 min and was monitored at 262 nm using photodiode array detection. After applying the forced degradation conditions, febuxostat degraded from 1.32 to 11.98% of its initial content. Statistical evaluation found that accuracy, precision, detection and quantitation limits, solution stability, and system suitability were acceptable. The lack of interfering degradation peaks ensured the stability-indicating nature of the method and method specificity. The application of three greenness metrics tools, such as the Green Analytical Procedure Index (GAPI), Analytical Greenness (AGREE) metrics, and analytical eco-scale (AES), revealed excellent method greenness. The current chromatographic method is apt for the routine quality control of febuxostat present in pharmaceutical formulations.