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Antipyretics, analgesics, bronchodilators, antitussives, expectorants, mucolytics, antihistamines, and antibiotics are among the pharmacological classes that are often administered either alone or in combination to treat and manage the symptoms attributed to upper respiratory tract disorders. In the rising era of green analytical chemistry, the development of broad, multi-analyte analytical techniques that can separate and quantify numerous pharmacologically related substances simultaneously is becoming of increasing significance. This work introduces a new, concise, accurate, and robust high performance liquid chromatography method with diode array detection approach for the simultaneous assay of eight substances, namely; Albuterol, Erdosteine, Paracetamol, Amoxicillin, Chlorpheniramine, Guaifenesin and two of the most frequently encountered preservatives that are incorporated in upper respiratory tract medications; Methyl and Propyl Parabens in their bulk and pharmaceutical formulations. An Inertsil octadecyl silane-3 (4.6\u2009\u00d7\u2009250\u00a0mm, 5\u00a0\u03bcm) column and a gradient mobile phase system consisting of methanol and 0.025\u00a0M potassium dihydrogen orthophosphate buffer (pH 4) were employed to achieve the separation. Chromatograms were detected at 225\u00a0nm for Albuterol and Chlorpheniramine, 230\u00a0nm for Guaifenesin and Amoxicillin, 236\u00a0nm for Erdosteine, 250\u00a0nm for Paracetamol, and 256\u00a0nm for Methyl and Propyl Parabens using the diode array detector. The suggested approach was successfully verified in compliance with the International Council for Harmonization guidelines with low values of percentage relative error and percentage relative standard deviation (&lt;\u20092%) and strong correlation coefficients (&gt;\u20090.9991), demonstrating its good accuracy, precision and linearity. Additionally, an in-depth five-sided examination was conducted to demonstrate the suggested method\u2019s greenness, blueness, violet innovation and sustainability profiles using the analytical GREEnness metric, analytical eco-scale, blue applicability grade index, click analytical chemistry index, violet innovation grade index and white analytical chemistry assessment metrics. This work represents the establishment of a broad spectrum, multianalyte, versatile methodology that would provide an indispensable asset for quality control laboratories in terms of its affordability, speed, sensitivity, and sustainability.<\/jats:p>","DOI":"10.1038\/s41598-026-45971-7","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:47:53Z","timestamp":1776091673000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sustainable multifaceted HPLC approach for concurrent quantitation of an octa-mixture used in upper respiratory therapy with a five-dimensional sustainability assessment"],"prefix":"10.1038","volume":"16","author":[{"given":"Hadeel A.","family":"Khalil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram G.","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feda A. 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