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Even for established drugs, it is necessary to maintain a cutting-edge impurity control system. To analyze caffeine and chlorphenoxamine hydrochloride in their binary mixture, as well as theophylline and chlorphenoxamine N-oxide as related substances, a reversed phase-high performance liquid chromatography combined with a diode array detector system was created. The chromatographic separation was conducted using a C18 X-select Waters\u00ae column. The mobile phase consisted of 20.0\u00a0mM potassium dihydrogen phosphate modified to pH 3 with o-phosphoric acid and methanol. A gradient elution program was adopted at a flow rate of 1.3\u00a0mL\/min and detected at a wavelength of 222\u00a0nm. The present methodology demonstrates a concentration ranging from 2\u201360, 1\u201380, 0.5\u201320 to 0.4\u201320\u00a0\u00b5g\/mL for chlorphenoxamine hydrochloride, caffeine, chlorphenoxamine N-Oxide and theophylline, respectively. Chlorphenoxamine N-Oxide, being an impurity of chlorphenoxamine was prepared by refluxing intact drug with 5% H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> for 24\u00a0h at 100\u00a0\u00b0C. One of the objectives of the analytical community is to promote the adoption of green analysis methods, which involve the development of environmentally friendly techniques. The levels of greenness and whiteness were evaluated using four specific tools: Eco-Scale System, GAPI, AGREE, and RGB tool. Furthermore, we have evaluated the greenness of the analytical method presented and compared its performance and greenness to that of the approach described in the literature. In this study, results from CPX and CAF analysis were compared to those obtained in a previous study. The result shows that there is no notable variation in precision and accuracy. The proposed method was validated in accordance with the requirements of ICH.<\/jats:p>","DOI":"10.1186\/s13065-024-01238-8","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T13:02:08Z","timestamp":1721394128000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel RP-HPLC\u2013DAD approach for simultaneous determination of chlorphenoxamine hydrochloride and caffeine with their related substances"],"prefix":"10.1186","volume":"18","author":[{"given":"Ahmed","family":"Ashraf","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norhan Badr","family":"ElDin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin","family":"Rostom","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badr A.","family":"El-Zeany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada A.","family":"Sedik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"1238_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12940-015-0057-0","volume":"14","author":"K Ito","year":"2015","unstructured":"Ito K, Weinberger KR, Robinson GS, Sheffield PE, Lall R, Mathes R, Ross Z, Kinney PL, Matte TD. 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