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Cited 97 times. https://www.journals.elsevier.com/talanta doi: 10.1016/j.talanta.2018.01.0130026265Xhttps://doi.org/10.1016/j.microc.2020.104893https://t.ly/Yi9FScopusView references (19) The effect of analytical procedures on the environment is a major concern nowadays. Scientists are trying to contribute to eco-friendly practices to reduce the negative impact of chemicals and solvents on the environment and analysts working on the field. This work demonstrates three chromatographic methods for the determination of a cold medication composed of dextromethorphan (DEX), phenylephrine (PHN) and brompheniramine (BRM) in their dosage form. Thin layer chromatography (TLC) was attempted using methanol: methylene chloride: water: acetic acid (7:1:1.5:0.5, v/v/v/v) as a mobile phase and detection carried out at 254 nm. The drugs were separated with good resolution at retention factors 0.54, 0.66 and 0.78 for BRM, DEX and PHN, respectively. Two high performance liquid chromatographic (HPLC) methods were also applied; method A utilized a mobile phase made up of acetonitrile, phosphate buffer and methanol (gradient elution) and green solvents were applied in method B namely; ethanol: water (15:85, v/v). Peaks were detected at 270 nm and the retention times for method A were 2.02, 7.59 and 8.43 min and for method B were 2.04, 4.25 and 4.91 min for PHN, BRM and DEX, respectively. Greenness profiles using three approaches; national environmental method index (NEMI), analytical ecoscale and green analytical procedure index (GAPI) were used to evaluate and compare the developed methods. Finally, statistical analysis was applied and no significant difference regarding accuracy and precision was noteden-USChromatographic methodsCold medicationGreenness profileArticlehttps://doi.org/10.1016/j.microc.2020.104893