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The Design of Experiments (DoE) strategy optimized the RP-HPLC method. The independent variables were buffer ratio, buffer pH, flow rate and injection volume. The dependent variables were retention time (Rt), Peak area, and resolution between the peaks of the analytes. The optimized conditions were: buffer ratio 68% and methanol 32%, flow rate 0.8 mL\/min, buffer pH 5.8, and injection volume 10 \u00b5L. The ICH Q2(R1) recommendations were followed in the validation of the optimized RP-HPLC method. The method demonstrated linearity of more than 0.99 for both ERT and LND. The LOD and LOQ were 0.75 and 1.62 ng\/mL for ERT; for LND 31.25 and 50 ng\/mL. The specificity of the established RP-HPLC method was unaffected by the MSNs matrix. The drugs-loaded MSNs were analyzed using the suggested RP-HPLC technique. The % entrapment efficiency of ERT and LND was found to be 72.65 and 79.50%, and drug loading of ERT and LND was found to be 14 and 17% in MSNs, respectively. The optimized RP-HPLC method was used to check the in-vitro drug release of the ERT and LND from the ERT-LND@MSNs. Surface properties of synthesized MSNs was checked through particle and SEM analysis. The developed analytical method was eco-friendly according to AGREE analysis and GAPI analysis.<\/jats:p>","DOI":"10.1038\/s41598-025-93331-8","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T12:25:57Z","timestamp":1741955157000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Quality by design based ecofriendly HPLC analytical method for simultaneous quantification of erastin and lenalidomide in mesoporous silica nanoparticles"],"prefix":"10.1038","volume":"15","author":[{"given":"Ashutosh","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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