Development and Validation of Green UV Spectrophotometric Method Using Augmented Classical Least Squares for Simultaneous Quantification of Atorvastatin, Ezetimibe, and Fenofibrate in Pharmaceutical and Environmental Samples

ABSTRACT

A novel UV‐spectrophotometric method employing spectral residual augmented classical least squares (SRACLS) and concentration residual augmented classical least squares (CRACLS) chemometric algorithms was developed and validated for simultaneous determination of three lipid‐lowering drugs: atorvastatin, ezetimibe, and fenofibrate. Severe spectral overlap across the 210–350 nm region necessitated advanced multivariate calibration approaches for quantitative resolution. A systematic experimental design strategy utilized a 25‐mixture partial factorial calibration set and an independent 20‐mixture central composite validation set, ensuring comprehensive coverage of the 4–12 µg/mL concentration range. Comparative evaluation demonstrated marked superiority of SRACLS over CRACLS, achieving higher linearity ( R ² = 0.991, 0.987, and 0.983), lower prediction errors (RMSEP = 1.0163, 1.6604, and 1.3750), and reduced bias for all three analytes. The optimized SRACLS method exhibited excellent recovery (99.37%–100.12%) for commercial pharmaceutical tablets with no significant differences from a reported HPLC method ( t ‐test, F ‐test, p > 0.05), and satisfactory recovery (95.47%–104.93%) for tap water samples following salting‐out‐assisted liquid–liquid extraction. Method validation according to ICH Q2(R2) guidelines confirmed acceptable accuracy, precision (RSD < 2%), and selectivity against pharmaceutical excipients and environmental contaminants. Comprehensive sustainability assessment using MoGAPI (74), CaFRI (83), BAGI (80.0), and RGB12 (86.5) demonstrated favorable greenness, minimal carbon footprint, and excellent practical applicability.