Analytical Method Development and Validation Based on Greenness Assessment and QBD Approach Using UV-Visible Spectrophotometric Method for Estimation of Ezetimibe

Objective: The aim of this study is to develop and validate a simple, economical, and eco-friendly method for analysis of Ezetimibe using UV-visible spectrophotometry and Quality-by-Design approach. Methods: This study defined an Analytical Target Profile and applied central-composite design to identify the parameters exerting the greatest influence on the response variable; solvent composition and wavelength were identified as the critical parameters, with absorbance as the response. Analysis of variance is used for the operational and statistical evaluation of the effects. All the system parameters and the chemicals used are green i. e. least toxic and eco-friendly to maintain sustainability. The green solvent used was ethanol: water (90:10 v/v) ratio. A UV-visible spectrophotometric method was developed based on Beer–Lambert's law and validated as per ICH Q2(R1) guidelines. Results: The developed method showed maximum absorbance at 232 nm, within the linearity range of 2-10 µg/ml and also yielded a correlation coefficient of R² = 0.9994. The recovery study shows values between 99-102%, whereas precision (0.365%), LOD (0.531µg/ml) and LOQ (1.61µg/ml) values are all obtained within the acceptable limit; robustness showed acceptable repeatability, though an assay-based bias trend warrants further investigation (see Limitations). The sustainability is also verified with a good score of 0.82 (out of 1.0) obtained from the AGREE tool. Conclusion: This study successfully employed a Quality-by-Design approach combined with UV-visible spectrophotometric analysis. This method proves suitable for determining Ezetimibe in the tested commercial formulation.