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The combined use of atypical antipsychotics; risperidone (RSP), and antidepressants medications; duloxetine hydrochloride (DLX), has grown more clinical significance in cutting edge treatments of complex psychiatric conditions like schizophrenia. This research targets to develop an environmentally harmonious, selective, and accurate TLC method to measure the levels of both DLX and RSP in spiked human plasma samples. A mixture of methanol, ethylacetate, and 33% ammonia solution (6: 4: 0.2, by volume) was successfully utilized as a solvent system to separate the proposed components. A UV-scanning wavelength of 230\u00a0nm was used for detection. An internal standard; propranolol (PRP); was used to account for small variations in the samples. The resulting retardation factors (R\n                    <jats:sub>f<\/jats:sub>\n                    ) were 0.02, 0.32, 0.46 and 0.59 for plasma, DLX, PRP and RSP, respectively. The linearity ranges were 0.04\u20130.4 and 0.1\u20130.6\u00a0\u00b5g band\n                    <jats:sup>\u2212\u20091<\/jats:sup>\n                    for DLX and RSP, respectively. The suggested method\u2019s environmental safety was evaluated using five tools and the results showed good greenness and blueness method\u2019s characteristics. Additionally, the method\u2019s figures of merits were within the accepted criteria, according to the US-FDA bio-analytical guidelines. Furthermore, drug-drug interactions (DDI) evaluation was conducted using web-based DDI tool to examine the interaction manifestations and to verify safety and therapeutic effectiveness of this combination.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1186\/s13065-025-01715-8","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T10:37:32Z","timestamp":1768991852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A green TLC\u2013densitometric bioanalytical method for concurrent determination of duloxetine and risperidone in human plasma with in-silico DDI evaluation"],"prefix":"10.1186","volume":"20","author":[{"given":"Fatma","family":"Magdy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raghda A.","family":"Emam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basma H.","family":"Anwar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"1715_CR1","first-page":"1821","volume":"75","author":"SH Schultz","year":"2007","unstructured":"Schultz SH, North SW, Shields CG. 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