An eco-friendly UV-spectrophotometric quantification of a spectrally overlapping mixture of felodipine and metoprolol in a pharmaceutical formulation: Evaluation of whiteness and greenness

• Ecofriendly, novel sensitive, accurate, precise spectrophotometric methods. • First derivative of ratio spectra, mean-centering, ratio-difference, and dual-wavelength methods. • Simultaneous determination of felodipine and metoprolol in pure samples. • Method application on pharmaceutical dosage form. • AGREE. MoGAPI, AGSA, and CaFRI calculators for green assessment of the methods. • RGBfast and CACI for whiteness and applicability assessment, respectively. According to the World Health Organization, cardiovascular diseases remain the world's leading cause of death. Beta blockers like metoprolol and calcium channel blockers like felodipine are commonly used in combination to enhance cardiovascular outcomes. Therefore, there is a pressing need for straightforward, eco-friendly techniques to quantify these compounds in their binary mixture. This work aims to develop and validate UV-spectrophotometric methods for the simultaneous determination of the selected compounds, overcoming the highly overlapping features and spectral interferences in the binary mixture. Namely, the proposed methods are Ratio-Derivative, Mean-Centering, Ratio-Difference, and Dual-Wavelength Spectrophotometry. For the validation of the four methods according to the ICH guidelines, linearity was achieved over concentration ranges of 0.30–15.00 µg/mL for felodipine and 0.40–22.00 µg/mL for metoprolol, with correlation coefficients of 0.9999. The detection and quantitation limits were below 0.12 µg/mL and 0.42 µg/mL, respectively. Mean recoveries ranged between 99.38 % and 100.00 %, and the RSD% values were all <2 %, confirming excellent accuracy and precision. The methods were found robust against ±1 nm wavelength variations. The developed methods were successfully applied for simultaneous quantification of the studied compounds in the pharmaceutical dosage form without interference from excipients. Four green metrics assessed the impact on the environment: AGREE, MoGAPI, AGSA, and CaFRI. Also, the whiteness and applicability of methods were assessed using RGB-fast and CACI methods, respectively. The proposed methods' simplicity, low cost, and greenness offer reliable, eco-friendly, and sustainable alternatives for the routine analysis of this combination.