Green chemometric approach for the simultaneous estimation of bupivacaine and meloxicam

A chemometric-assisted UV–Vis spectrophotometric method was developed and validated for the simultaneous determination of bupivacaine (BUP) and meloxicam (MEL) in bulk drug substances and laboratory-synthesized mixtures. Owing to the severe spectral overlap between the two analytes, multivariate calibration models including Principal Component Regression (PCR), Partial Least Squares (PLS), and Artificial Neural Network (ANN) regression were constructed using full-spectrum absorbance data recorded over the 250–400 nm range and generated through a 72 full factorial experimental design. The developed models demonstrated excellent analytical performance, with mean recovery values of 99.1% for BUP and 100.2% for MEL and relative standard deviation values below 3%, confirming high accuracy and precision. Strong predictive ability was evidenced by low RMSEP values (0.35–0.38 for BUP and 0.68–1.01 for MEL). External validation, statistical comparison with a reported method using Student’s t-test and F-test, and ICH Q2(R2)-compliant validation parameters confirmed the robustness, selectivity, and reliability of the proposed approach. Among the evaluated models, PCR and PLS exhibited superior interpretability and sensitivity, while ANN effectively addressed spectral non-linearity. From a sustainability perspective, the method aligns strongly with green and white analytical chemistry principles by eliminating chromatographic separation, minimizing solvent consumption, reducing waste generation, and lowering energy demand through the use of UV–Vis spectrophotometry. Environmental and practical performance was comprehensively assessed using multiple complementary tools, including the Analytical Eco-Scale, RGB12 whiteness assessment (overall score: 88.88%), AGREE metric (score: 0.85), Environmental and Practical Performance Index (EPPI = 0.865), and the recently developed Multi-color Assessment (MA) tool for white analytical chemistry, confirming balanced analytical performance, environmental friendliness, practicality, and innovation. Overall, the proposed chemometric UV–Vis strategy provides a robust, sustainable, and cost-effective alternative to conventional chromatographic methods, offering a reliable and eco-friendly solution for routine pharmaceutical quality control of bupivacaine and meloxicam.