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Preliminary screening trials along with systemic risk analysis were performed, endeavouring to explicate the critical method attributes, namely pH, percentage of orthophosphoric acid and percentage of acetonitrile, that influence the critical quality attributes. Box\u2013Behnken design was utilized for the optimization of the tailing factor as the response for MTX and BCL in a short run time. The chromatographic conditions were optimized by performing 17 experimental runs using design expert software. The chromatographic conditions were selected after the analysis of the optimized zone within the confines of the design space: water:acetonitrile adjusted to a pH of 3.0 with 0.05% orthophosphoric acid (60:40, %v\/v) was the mobile phase, the flow rate was 1.0\u00a0ml\/min and an analytical C\n                    <jats:sub>18<\/jats:sub>\n                    column was used at an isobestic wavelength of 282\u2009nm. Furthermore, the optimized method was validated in accordance with the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines and was found to be within the prescribed limits. Therefore, the developed reversed\u2010phase\u2010high\u2010performance liquid chromatography method has a high degree of practical utility for synchronous detection of MTX and BCL in pharmaceutical nano\u2010dosage forms such as protein\u2010based nanoparticles, nanocrystals, polymeric nanoparticles and metallic nanoparticles in\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies.\n                  <\/jats:p>","DOI":"10.1002\/bmc.5581","type":"journal-article","created":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T06:28:55Z","timestamp":1673072935000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Application of QbD based approach in development and validation of RP\u2010HPLC method for simultaneous estimation of methotrexate and baicalin in dual\u2010drug\u2010loaded liposomes"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7857-1124","authenticated-orcid":false,"given":"Syeda Nashvia","family":"Adin","sequence":"first","affiliation":[{"name":"Phytomedicine Laboratory, Department of Pharmacognosy and Phytochemistry School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-2967","authenticated-orcid":false,"given":"Isha","family":"Gupta","sequence":"additional","affiliation":[{"name":"Phytomedicine Laboratory, Department of Pharmacognosy and Phytochemistry School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6797-3104","authenticated-orcid":false,"given":"Mohd","family":"Aqil","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-780X","authenticated-orcid":false,"given":"Mohd","family":"Mujeeb","sequence":"additional","affiliation":[{"name":"Phytomedicine Laboratory, Department of Pharmacognosy and Phytochemistry School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00764-022-00182-4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/pm.pm_160_22"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.14978"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.5530\/097484900279"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0039-9140(00)00514-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.03.004"},{"key":"e_1_2_8_8_1","unstructured":"Guideline IHT. 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