Application of Box-Behnken design combined response surface methodology to optimize HPLC and spectrophotometric techniques for quantifying febuxostat in pharmaceutical formulations and spiked wastewater samples

This study applied an optimized Box-Behnken Design (BBD) to develop visible spectrophotometry and a high-performance liquid chromatography (HPLC) method for quantitating febuxostat (FBX) in pharmaceutical prep-arations and spiked wastewater samples. A visible spectrophotometric method was developed by the reaction of FBX with a universal oxidant, potassium permanganate (KMnO4), in alkaline media, absorbed at 605 nm was exploited to determine FBX in pharmaceutical preparations. While the BBD was used to optimize the most sig-nificant factors that influenced the chromatographic analysis for quantifying FBX. The calibration plot was linear between 0.1 and 6.4 mu g/mL for HPLC and 0.75-11.8 mu g/mL for the spectrophotometric method. BBD is an effective design for optimizing reaction conditions to minimize the number of experiments and the cost of the method. Response Surface Methodology (RSM) via BBD optimized the chromatographic procedure. The inter-national conference on harmonization (ICH) guidelines evaluated validation parameters linearity, precision, accuracy, detection limits, and quantitation. Furthermore, Youden's robustness test using factorial combinations of the chosen analytical parameters was performed and investigated the influence of alternative conditions. The simplicity of the spectrophotometric and HPLC methods suggests their practical use in the quality control analysis of febuxostat. Moreover, it is economical, consumes a minimum amount of organic solvent, and has good accuracy and precision.

Automated summary

This study developed visible spectrophotometry and high-performance liquid chromatography (HPLC) methods for quantitating febuxostat. The methods showed good accuracy and precision through optimization of reaction conditions and the chromatographic process.