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These proposed approaches provide reliable, low-cost, and accessible alternatives to conventional chromatographic techniques, which often require complex instrumentation, extended analysis times, and significant solvent consumption. Two complementary spectrophotometric methods were established. Method A, the ratio-difference approach, utilized MEL as a divisor for the quantification of SAX, while SAX served as a divisor for determining MET and MEL. Method B, based on the first derivative of ratio spectra, applied MEL as a divisor under optimized conditions (scaling factor\u2009=\u200910, \u0394\u03bb\u2009=\u20094\u00a0nm). However, MEL could not be quantified by Method B because its derivative ratio signals in the selected spectral region were too weak and overlapped extensively with those of SAX and MET, preventing the establishment of a reliable linear calibration curve for this impurity. The methods exhibited linearity over the ranges of 5\u201390\u202f\u00b5g\/mL for SAX, 1\u201340\u202f\u00b5g\/mL for MET, and 0.5\u201310\u202f\u00b5g\/mL for MEL. Validation in accordance with ICH Q2(R1) guidelines confirmed their accuracy, precision, selectivity, and specificity. The results obtained by the proposed methods were statistically compared with those of a reported RP\u2011HPLC method, confirming the reliability of the proposed procedures. The environmental impact was assessed using the principles of green analytical chemistry (GAC), which incorporates sustainability by promoting methods that limit hazardous reagents, reduce energy consumption, and minimize waste while maintaining suitable analytical performance. Holistic evaluation tools such as the analytical greenness metric (AGREE), the green analytical procedure index (GAPI), the national environmental methods index (NEMI), the blue applicability grade index (BAGI), and the RGB 12 model enable simultaneous assessment of analytical quality, environmental impact, and practical applicability. These tools foster the development of \u201cwhite\u201d analytical chemistry and complement emerging indices like the environmental and practical performance index (EPPI).Overall, these spectrophotometric approaches represent sustainable, efficient, and accessible analytical alternatives for the routine quality control of Saxagliptin and Metformin in combined pharmaceutical formulations.<\/jats:p>","DOI":"10.1038\/s41598-026-38952-3","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T11:02:55Z","timestamp":1774090975000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Eco-friendly spectrophotometric approach for the determination of anti-diabetic drugs in fixed-dose formulation together with metformin\u2019s toxic impurity: comprehensive method assessment"],"prefix":"10.1038","volume":"16","author":[{"given":"Doaa G.","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha M.","family":"Abdelrahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal B.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maimana A.","family":"Magdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"38952_CR1","volume-title":"Clarke\u2019s Analysis of Drugs and Poisons","author":"AC Moffat","year":"2011","unstructured":"Moffat, A. 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