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• Straightforward, sensitive, and precise UPLC and Spectroscopic were employed to develop environmentally-conscious techniques for detecting timolol maleate (TIM), dorzolamide HCl (DOR), and benzalkonium Cl (BNZ) simultaneously. • The pursuit of sustainable solutions is increasingly crucial in contemporary times. We propose inventive research that fulfills the criteria of whiteness and greenness in analytical chemistry. • We aim to develop eco-friendly techniques for detecting timolol maleate (TIM), dorzolamide HCl (DOR), and benzalkonium Cl (BNZ) simultaneously by using sustainable spectroscopic methods with purified water and ethanol as alternative solvents. • The approach exhibited exceptional selectivity and sensitivity, making it suitable for conducting bioequivalence, pharmacokinetics, drug-drug interaction, and pharmacodynamics studies. • The method's advantage lies in its amalgamation of a straightforward sample preparation technique, a small injection volume, and a brief runtime. The pursuit of sustainable solutions is increasingly crucial in contemporary times. We propose inventive research that fulfills the criteria of whiteness and greenness in analytical chemistry. The endeavor aims to advance environmentally conscious techniques for the simultaneous detection of timolol maleate (TIM), dorzolamide HCl (DOR), and benzalkonium Cl (BNZ). The first method employed a sustainable mobile phase consisting of 0.02 M phosphate buffer: ethanol (68:32, v/v), and a flow rate of 0.6 mL/min with retention times 1.274, 1.798, and 2.483 min for DOR, TIM, and BNZ, respectively, with a UV detector at 210 nm. This methodology was easy, fast, and accurate. The approach showed low processing times, peak symmetry, and satisfactory resolution, with correlation values of 0.999. The linearity was between 0.001–0.064, 0.001–0.060 µg mL -1 , and 0.001–0.050 µg mL -1 for DOR, TIM, and BNZ, respectively. Furthermore, employing water as the solvent, complementary spectrophotometric methods such as Mean Centering of Ratio Spectra (MCR) and Successive Derivative Ratio Spectra (SRDS) were investigated as economical and environmentally friendly substitutes. All procedures demonstrated good linearity (r² > 0.9990), acceptable accuracy, and precision (RSD ≤ 2 %). Furthermore, by proving the superiority of the current work over previously published methods regarding sustainability, analytical performance, economics, and practicality, the real-world implementation of four greenness and whiteness algorithms boosts the approval and overall sustainable development of the proposed methods. The suggested techniques offer low-cost, environmentally friendly substitutes for traditional methods, advancing the field of analytical chemistry towards more sustainable practices and fostering a less destructive future for quality control.