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The use of sodium dodecyl sulfate surfactant at pH 7 enhances the fluorescence intensity of diphenhydramine at 286 nm (method I) enabling its nanodetermination in biological samples with mean per cent recovery \u00b1 SD of 100.33 \u00b1 1.519. Method I was validated according to ICH\u2010Q2R1 guidelines and was successfully applied for determination of diphenhydramine in pharmaceutical dosage form and spiked human plasma in the concentration ranges 0.1\u20134.0 \u03bcg\/mL and 0.2\u20131.0 \u03bcg\/mL, respectively. Method I acted as a basis for the development of a first derivative synchronous spectrofluorimetry (method II) for simultaneous analysis of diphenhydramine and naproxen using a zero\u2010crossing approach. Method II determines both drugs with linearity ranges of 0.05\u20133.0 \u03bcg\/mL and 0.1\u20130.9 \u03bcg\/mL for diphenhydramine and naproxen, respectively. The developed method was applied for the simultaneous determination of both drugs in their laboratory\u2010prepared mixtures containing all expected excipients. Method II determines both drugs with a mean percent recovery \u00b1 SD of 100.56 \u00b1 0.891 and 100.20 \u00b1 1.125 for diphenhydramine and naproxen, respectively. The method was statistically compared with a reported method using Student's <jats:italic>t<\/jats:italic>\u2010 and F\u2010 tests, and no significant differences were observed.<\/jats:p>","DOI":"10.1002\/bio.3996","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T05:22:14Z","timestamp":1608268934000},"page":"733-741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Micelle\u2010enhanced spectrofluorimetric determination of diphenhydramine: application to human plasma and its simultaneous determination with naproxen in pharmaceutical tablets"],"prefix":"10.1002","volume":"36","author":[{"given":"Sherin F.","family":"Hammad","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy Tanta University, The Medical Campus of Tanta University  Elgeish Street Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-0771","authenticated-orcid":false,"given":"Basma Z.","family":"El\u2010Khateeb","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy Tanta University, The Medical Campus of Tanta University  Elgeish Street Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah F.","family":"El\u2010Malla","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy Tanta University, The Medical Campus of Tanta University  Elgeish Street Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,10]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Clarke's Analysis of Drugs and Poisons","author":"Moffat A. 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