An eco-friendly chemometrics assisted UV spectrophotometric method for simultaneous determination of sofosbuvir, simeprevir and ledipasvir in pharmaceuticals.

Abstract

This study develops and validates an eco-friendly ultraviolet (UV)-spectrophotometric method employing augmented least squares chemometric models for the simultaneous determination of three hepatitis C antiviral drugs-sofosbuvir, simeprevir, and ledipasvir. Two multivariate approaches were compared: Concentration Residual Augmented Classical Least Squares (CRACLS) and Spectral Residual Augmented Classical Least Squares (SRACLS). The experimental design utilized a 5-level partial factorial design for calibration (25 samples) and a central composite design for validation (20 samples). SRACLS models demonstrated superior analytical performance with lower detection limits (0.5171, 0.5175, 0.2950 μg/mL), higher precision (relative bias corrected mean square error of prediction, RBCMSEP: 0.1481-0.2509%), and better predictive capability (relative root mean square error of prediction, RRMSEP: 1.0285%, 1.2668%, 1.8933%) compared to CRACLS models (RRMSEP: 3.0655%, 1.9264%, 2.7201%). The SRACLS models also exhibited lower complexity with fewer principal components (3, 2, and 3) versus CRACLS iterations (4, 4, and 6). Application to commercial pharmaceuticals yielded excellent recoveries (99.70-100.39%) with no statistically significant difference from reference high-performance liquid chromatography (HPLC) methods. Greenness assessment confirmed the method's environmental advantages with superior scores in multiple sustainability metrics (Analytical GREEnness metric, AGREE: 0.75; Modified Green Analytical Procedure Index, MOGAPI: 78; RGB12 whiteness score: 94.2) compared to conventional chromatographic techniques (AGREE: 0.63-0.65, MOGAPI: 66-72, RGB12: 76.9-83.3). These findings establish the proposed method as a rapid, sensitive, and eco-friendly alternative for routine quality control of these critical hepatitis C drugs.