{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:50:08Z","timestamp":1788295808028,"version":"build-2803163510"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Science, Technology & Innovation Funding Authority"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A green RP-HPLC approach coupled with spectrofluorometric detection was established for the simultaneous estimation of the co-administered drugs Azelastine (AZL) and Losartan (LOS) in spiked human plasma samples. Preliminary trials were carried out for determination of the Critical Method Parameters (CMPs) and Critical Quality Attributes (CQAs). Design of Experiment (DOE) was developed relying on the use of Central Composite Design (CCD)\u00a0for the optimization of conditions to establish a simple, rapid, cost-effective and environmentally benign approach. The chromatographic separation was based on using a mobile phase composed of methanol: acetonitrile: 0.02M phosphate buffer of pH 3.25 with 0.05% tri-ethylamine (60: 1.5: 38.5, v\/v\/v) at a flow rate of 1.2\u00a0mL\/min and injection volume of 10\u00b5L. The fluorescence detection was carried out at 245 nm\/400 nm and 290 nm\/360 nm for estimation of LOS and AZL, respectively. The retention times of AZL and LOS were 8.9\u2009\u00b1\u20090.2 min and 13.4\u2009\u00b1\u20090.1 min, respectively. The developed method was validated according to ICH Guidelines with linear relationship in concentration ranges of 0.10\u201350.0\u00b5g\/mL for AZL and 0.30\u201340.0\u00b5g\/mL for LOS, while in spiked plasma samples the concentration ranges were 0.025\u20130.07\u00b5g\/mL for AZL and 0.025\u20130.10 \u00b5g\/mL for LOS. The developed approach was successfully applied for the quantitation of both drugs in spiked human plasma samples. Complex MoGAPI and AGREE methodologies were used for greenness assessment.<\/jats:p>","DOI":"10.1038\/s41598-026-39426-2","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:46:56Z","timestamp":1772610416000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Green DOE based RP-HPLC method for the simultaneous determination of Azelastine and Losartan in spiked human plasma samples"],"prefix":"10.1038","volume":"16","author":[{"given":"Aya","family":"Roshdy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fathalla","family":"Belal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya A.","family":"Marie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"39426_CR1","doi-asserted-by":"publisher","first-page":"20160025","DOI":"10.1515\/revac-2016-0025","volume":"36","author":"SB Ganorkar","year":"2017","unstructured":"Ganorkar, S. B. & Shirkhedkar, A. A. Design of experiments in liquid chromatography (HPLC) analysis of pharmaceuticals: Analytics, applications, implications and future prospects. Rev. Anal. Chem. 36, 20160025 (2017).","journal-title":"Rev. Anal. Chem."},{"key":"39426_CR2","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.jpba.2018.06.018","volume":"158","author":"B Sylvester","year":"2018","unstructured":"Sylvester, B., Tefas, L., Vlase, L., Tomu\u0163\u0103, I. & Porfire, A. A Quality by Design (QbD) approach to the development of a gradient high-performance liquid chromatography for the simultaneous assay of curcuminoids and doxorubicin from long-circulating liposomes. J. Pharm. Biomed. Anal. 158, 395\u2013404 (2018).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"39426_CR3","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1194\/jlr.R900010-JLR200","volume":"50","author":"JY Chiang","year":"2009","unstructured":"Chiang, J. Y. Bile acids: Regulation of synthesis: Thematic review series: Bile acids. J. Lipid Res. 50, 1955\u20131966 (2009).","journal-title":"J. Lipid Res."},{"key":"39426_CR4","doi-asserted-by":"crossref","unstructured":"Cartwright, A. C. The British pharmacopoeia, 1864 to 2014: medicines, international standards and the state. (Routledge, 2016).","DOI":"10.4324\/9781315614182"},{"key":"39426_CR5","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1097\/ACI.0b013e3283303ebb","volume":"9","author":"A Lambiase","year":"2009","unstructured":"Lambiase, A., Micera, A. & Bonini, S. Multiple action agents and the eye: do they really stabilize mast cells?. Curr. Opin. Allergy Clin. Immunol. 9, 454\u2013465 (2009).","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"39426_CR6","first-page":"29","volume":"3","author":"AA Gouda","year":"2015","unstructured":"Gouda, A. A., El Sheikh, R. & El Saied, H. Extractive spectrophotometric determination of azelastine hydrochloride in pure form and pharmaceutical formulations. Cand. Chem. Trans. 3, 29\u201341 (2015).","journal-title":"Cand. Chem. Trans."},{"key":"39426_CR7","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.saa.2017.10.049","volume":"191","author":"AA El-Masry","year":"2018","unstructured":"El-Masry, A. A., Hammouda, M. E., El-Wasseef, D. R. & El-Ashry, S. M. Validated spectroscopic methods for determination of anti-histaminic drug azelastine in pure form: Analytical application for quality control of its pharmaceutical preparations. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 191, 413\u2013420 (2018).","journal-title":"Spectrochim. Acta Part A: Mol. Biomol. Spectrosc."},{"key":"39426_CR8","first-page":"48","volume":"2","author":"M Hassouna","year":"2017","unstructured":"Hassouna, M., Abdelrahman, M. M. & Mohamed, M. A. Determination of azelastine hydrochloride and benzalkonium chloride in their ophthalmic solution by different spectrophotometric methods. World J. Appl. Chem. 2, 48\u201356 (2017).","journal-title":"World J. Appl. Chem."},{"key":"39426_CR9","first-page":"13","volume":"49","author":"NN Salama","year":"2011","unstructured":"Salama, N. N., Abdel-Razeq, S. A., Abdel-Atty, S. & El-Kosy, N. Spectrophotometric determination and thermodynamic studies of the charge transfer complexes of azelastine-HCl. Bull. Fac. Pharm., Cairo Univ. 49, 13\u201318 (2011).","journal-title":"Bull. Fac. Pharm., Cairo Univ."},{"key":"39426_CR10","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.saa.2016.02.010","volume":"160","author":"HA Merey","year":"2016","unstructured":"Merey, H. A., El-Mosallamy, S. S., Hassan, N. Y. & El-Zeany, B. A. Simultaneous determination of fluticasone propionate and azelastine hydrochloride in the presence of pharmaceutical dosage form additives. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 160, 50\u201357 (2016).","journal-title":"Spectrochim. Acta Part A: Mol. Biomol. Spectrosc."},{"key":"39426_CR11","first-page":"1173","volume":"3","author":"A Reda","year":"2024","unstructured":"Reda, A., Saleh, H., Bahgat, E. A. & Fawzy, M. G. Analytical methods for determination of azelastine hydrochloride and fluticasone propionate in different matrices: A mini review. ERU Res. J. 3, 1173\u20131187 (2024).","journal-title":"ERU Res. J."},{"key":"39426_CR12","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.saa.2018.06.057","volume":"204","author":"MA Ragab","year":"2018","unstructured":"Ragab, M. A. & Eman, I. Investigation of the spectrofluorimetric behavior of azelastine and nepafenac: Determination in ophthalmic dosage forms. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 204, 260\u2013266 (2018).","journal-title":"Spectrochim. Acta Part A: Mol. Biomol. Spectrosc."},{"key":"39426_CR13","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1007\/s10812-021-01224-1","volume":"88","author":"S Shekhar","year":"2021","unstructured":"Shekhar, S. & Bali, A. Spectrofluorimetric method for the determination of azelastine hydrochloride in bulk and nasal formulations. J. Appl. Spectrosc. 88, 674\u2013680 (2021).","journal-title":"J. Appl. Spectrosc."},{"key":"39426_CR14","doi-asserted-by":"publisher","first-page":"120","DOI":"10.59566\/IJBS.2010.6120","volume":"6","author":"Y-S Park","year":"2010","unstructured":"Park, Y.-S. et al. Determination of azelastine in human plasma by validated liquid chromatography coupled to tandom mass spectrometry (LC-ESI\/MS\/MS) for the clinical studies. Int. J. Biomed. Sci. 6, 120 (2010).","journal-title":"Int. J. Biomed. Sci."},{"key":"39426_CR15","first-page":"555","volume":"1","author":"M Hassouna","year":"2017","unstructured":"Hassouna, M., Abdelrahman, M. & Abdelfatah, M. Simultaneous determination of azelastine hydrochloride and benzalkonium chloride by RP-HPLC method in their ophthalmic solution. J. Forensic Sci. Crim. Investig. 1, 555\u2013565 (2017).","journal-title":"J. Forensic Sci. Crim. Investig."},{"key":"39426_CR16","doi-asserted-by":"publisher","first-page":"76","DOI":"10.31788\/RJC.2023.1616916","volume":"16","author":"A Gupta","year":"2023","unstructured":"Gupta, A., Singour, P. & Jain, S. Simultaneous reverse phase-high performance liquid chromatography (RP-HPLC) estimation of azelastine hydrochloride, fluticasone propionate, and phenyl ethyl alcohol in dymista (MEDA) nasal spray. Rasayan J. Chem. 16, 76\u201384 (2023).","journal-title":"Rasayan J. Chem."},{"key":"39426_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-024-82387-7","volume":"15","author":"NN Mikawy","year":"2025","unstructured":"Mikawy, N. N., Magdy, N., Mohamed, M. H. & El-Kosasy, A. M. Validated HPLC method for simultaneous determination of azelastine hydrochloride fluticasone propionate and oxymetazoline in nasal mucosa and nasopharyngeal swabs from real human samples. Sci. Rep. 15, 1\u201310 (2025).","journal-title":"Sci. Rep."},{"key":"39426_CR18","doi-asserted-by":"publisher","first-page":"236","DOI":"10.22270\/jddt.v8i6-s.2222","volume":"8","author":"CH Gill","year":"2018","unstructured":"Gill, C. H. et al. A study of method development and validation for estimation of Azelastine hydrochloride in nasal spray formulations by RP-HPLC method. J. Drug Deliv. Ther. 8, 236\u2013240 (2018).","journal-title":"J. Drug Deliv. Ther."},{"key":"39426_CR19","doi-asserted-by":"publisher","first-page":"22435","DOI":"10.1038\/s41598-022-26774-y","volume":"12","author":"WN Abd-AlGhafar","year":"2022","unstructured":"Abd-AlGhafar, W. N., Aly, F. A., Sheribah, Z. A. & Saad, S. Factorial design-assisted reverse phase HPLC\u2013UV approach for the concurrent estimation of cetirizine and azelastine in aqueous humor. Sci. Rep. 12, 22435 (2022).","journal-title":"Sci. Rep."},{"key":"39426_CR20","doi-asserted-by":"publisher","first-page":"248","DOI":"10.22159\/ajpcr.2018.v11i8.25506","volume":"11","author":"S Patel","year":"2018","unstructured":"Patel, S. & Pasha, T. Stability-indicating high-performance liquid chromatography method for determination of antihistamine drug azelastine. Asian J. Pharm. Clin. Res 11, 248\u2013251 (2018).","journal-title":"Asian J. Pharm. Clin. Res"},{"key":"39426_CR21","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1111\/jphp.13363","volume":"72","author":"MM Elseweidy","year":"2020","unstructured":"Elseweidy, M. M., Elnagar, G. M., Elsawy, M., Ali, A. A. & Zein, N. Losartan and azelastine either alone or in combination as modulators for endothelial dysfunction and platelets activation in diabetic hyperlipidemic rats. J. Pharm. Pharmacol. 72, 1812\u20131821 (2020).","journal-title":"J. Pharm. Pharmacol."},{"key":"39426_CR22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/bs.podrm.2015.02.003","volume":"40","author":"A-RA Al-Majed","year":"2015","unstructured":"Al-Majed, A.-R.A., Assiri, E., Khalil, N. Y. & Abdel-Aziz, H. A. Losartan: Comprehensive profile. Profiles Drug Subst., Excip. Relat. Methodol. 40, 159\u2013194 (2015).","journal-title":"Profiles Drug Subst., Excip. Relat. Methodol."},{"key":"39426_CR23","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s11239-005-0343-8","volume":"18","author":"S Nomura","year":"2004","unstructured":"Nomura, S. et al. Losartan and simvastatin inhibit platelet activation in hypertensive patients. J. Thromb. Thrombolysis 18, 177\u2013185 (2004).","journal-title":"J. Thromb. Thrombolysis"},{"key":"39426_CR24","first-page":"250","volume":"24","author":"VM dos Passos","year":"2005","unstructured":"dos Passos, V. M., DIAS, C. L. & Bergold, A. M. Validation of an isocratic HPLC assay of losartan potassium in pharmaceutical formulations and stress test for stability evaluation of drug substance. Acta Farm Bonaerense 24, 250\u2013255 (2005).","journal-title":"Acta Farm Bonaerense"},{"key":"39426_CR25","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/S0039-9140(01)00379-4","volume":"54","author":"E Cagigal","year":"2001","unstructured":"Cagigal, E., Gonzalez, L., Alonso, R. & Jimenez, R. Experimental design methodologies to optimise the spectrofluorimetric determination of Losartan and Valsartan in human urine. Talanta 54, 1121\u20131133 (2001).","journal-title":"Talanta"},{"key":"39426_CR26","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/bio.2689","volume":"30","author":"F Demirkaya-Miloglu","year":"2015","unstructured":"Demirkaya-Miloglu, F., Yaman, M. E. & Kadioglu, Y. A new spectrofluorimetric method for determination of losartan potassium in rabbit plasma and its application to pharmacokinetic study. Luminescence 30, 53\u201359 (2015).","journal-title":"Luminescence"},{"key":"39426_CR27","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1590\/S1984-82502014000300021","volume":"50","author":"F Demirkaya-Miloglu","year":"2014","unstructured":"Demirkaya-Miloglu, F., Yaman, M. E. & Kadioglu, Y. Optimization of a spectrofluorimetric method based on a central composite design for the determination of potassium losartan in pharmaceutical products. Braz. J. Pharm. Sci. 50, 611\u2013619 (2014).","journal-title":"Braz. J. Pharm. Sci."},{"key":"39426_CR28","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1007\/s10812-015-0190-0","volume":"82","author":"M Taher","year":"2015","unstructured":"Taher, M., Asadollahzadeh, H. & Fazelirad, H. A simple spectrofluorimetric method for the determination of losartan in some tablet dosage forms. J. Appl. Spectrosc. 82, 842\u2013844 (2015).","journal-title":"J. Appl. Spectrosc."},{"key":"39426_CR29","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1590\/S1984-82502010000100017","volume":"46","author":"R Bonfilio","year":"2010","unstructured":"Bonfilio, R. et al. Comparative study of analytical methods by direct and first-derivative UV spectrophotometry for evaluation of losartan potassium in capsules. Braz. J. Pharm. Sci. 46, 147\u2013155 (2010).","journal-title":"Braz. J. Pharm. Sci."},{"key":"39426_CR30","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0731-7085(03)00347-9","volume":"33","author":"OC Lastra","year":"2003","unstructured":"Lastra, O. C., Lemus, I. G., S\u00e1nchez, H. J. & P\u00e9rez, R. F. Development and validation of an UV derivative spectrophotometric determination of Losartan potassium in tablets. J. Pharm. Biomed. Anal. 33, 175\u2013180 (2003).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"39426_CR31","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.saa.2014.09.007","volume":"136","author":"L Abdel-Fattah","year":"2015","unstructured":"Abdel-Fattah, L., Abdel-Aziz, L. & Gaied, M. Enhanced spectrophotometric determination of Losartan potassium based on its physicochemical interaction with cationic surfactant. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc. 136, 178\u2013184 (2015).","journal-title":"Spectrochim. Acta Part A: Mol. Biomol. Spectrosc."},{"key":"39426_CR32","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4103\/0250-474X.62243","volume":"72","author":"KS Rao","year":"2010","unstructured":"Rao, K. S. & Srinivas, K. RP-HPLC method for the determination of losartan potassium and ramipril in combined dosage form. Indian J. Pharm. Sci. 72, 108 (2010).","journal-title":"Indian J. Pharm. Sci."},{"key":"39426_CR33","first-page":"227","volume":"10","author":"NMS Mohammed","year":"2019","unstructured":"Mohammed, N. M. S., Abdo, H. R. & Hassan, H. M. Method development and validation of simultaneous determination of hydrochlorothiazide and losartan in tablet dosage form by RP-HPLC. Int. J. Pharm. Sci. Res. 10, 227\u2013231 (2019).","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"39426_CR34","first-page":"521","volume":"1","author":"K Kathiresan","year":"2008","unstructured":"Kathiresan, K., Gothandaraman, S., Manickam, M., Kumar, S. & Manavalan, R. Analytical method development and validation of losartan potassium tablet by RP-HPLC. Rasayan J. Chem. 1, 521\u2013525 (2008).","journal-title":"Rasayan J. Chem."},{"key":"39426_CR35","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/736761","volume":"2014","author":"HA Pawar","year":"2014","unstructured":"Pawar, H. A. & Lalitha, K. Development and validation of a novel RP-HPLC method for estimation of losartan potassium in dissolution samples of immediate and sustained release tablets. Chromatogr. Res. Int. 2014, 736761 (2014).","journal-title":"Chromatogr. Res. Int."},{"key":"39426_CR36","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.amjcard.2006.01.059","volume":"98","author":"CM Ferrario","year":"2006","unstructured":"Ferrario, C. M. & Strawn, W. B. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am. J. Cardiol. 98, 121\u2013128 (2006).","journal-title":"Am. J. Cardiol."},{"key":"39426_CR37","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s11239-005-0343-8","volume":"18","author":"S Nomura","year":"2004","unstructured":"Nomura, S. et al. Losartan and simvastatin inhibit platelet activation in hypertensive patients. J. Thromb. Thrombolysis 18, 177\u2013185 (2004).","journal-title":"J. Thromb. Thrombolysis"},{"key":"39426_CR38","unstructured":"ICH Harmonised Tripartite Guidelines, Validation of analytical procedures: text and methodology Q2(R1). http:\/\/www.ich.org\/products\/guidelines\/quality\/article\/quality-guidelines.html (Accessed 24.01.2026). Ref Type: Electronic Citation. (2013)."},{"key":"39426_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2023.117196","volume":"166","author":"LP Kowtharapu","year":"2023","unstructured":"Kowtharapu, L. P., Katari, N. K., Muchakayala, S. K. & Marisetti, V. M. Green metric tools for analytical methods assessment critical review, case studies and crucify. Trends Anal. Chem. 166, 117196 (2023).","journal-title":"Trends Anal. Chem."},{"key":"39426_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2021.106685","volume":"170","author":"KP Kannaiah","year":"2021","unstructured":"Kannaiah, K. P., Sugumaran, A., Chanduluru, H. K. & Rathinam, S. Environmental impact of greenness assessment tools in liquid chromatography\u2013A review. Microchem. J. 170, 106685 (2021).","journal-title":"Microchem. J."},{"key":"39426_CR41","doi-asserted-by":"publisher","first-page":"117211","DOI":"10.1016\/j.trac.2023.117211","volume":"166","author":"M Shi","year":"2023","unstructured":"Shi, M. et al. Overview of sixteen green analytical chemistry metrics for evaluation of the greenness of analytical methods. Trends Anal. Chem. 166, 117211 (2023).","journal-title":"Trends Anal. Chem."},{"key":"39426_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.greeac.2024.100126","volume":"10","author":"FR Mansour","year":"2024","unstructured":"Mansour, F. R., Omer, K. M. & P\u0142otka-Wasylka, J. A total scoring system and software for complex modified GAPI (ComplexMoGAPI) application in the assessment of method greenness. Green Anal. Chem. 10, 100126 (2024).","journal-title":"Green Anal. Chem."},{"key":"39426_CR43","doi-asserted-by":"publisher","first-page":"10076","DOI":"10.1021\/acs.analchem.0c01887","volume":"92","author":"F Pena-Pereira","year":"2020","unstructured":"Pena-Pereira, F., Wojnowski, W. & Tobiszewski, M. AGREE\u2014Analytical GREEnness metric approach and software. Anal. Chem. 92, 10076\u201310082 (2020).","journal-title":"Anal. Chem."},{"key":"39426_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.greeac.2024.100178","volume":"12","author":"TA Zughaibi","year":"2025","unstructured":"Zughaibi, T. A. & Al-Asmari, A. I. Study of adsorption potential of cellulose paper for abusable prescription drug analysis: A practical and sustainable approach validated by BAGI and ComplexMoGAPI tools. Green Anal. Chem. 12, 100178 (2025).","journal-title":"Green Anal. Chem."},{"key":"39426_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.sampre.2025.100164","volume":"14","author":"FR Mansour","year":"2025","unstructured":"Mansour, F. R., Bedair, A. & Locatelli, M. Click Analytical Chemistry Index as a novel concept and framework, supported with open source software to assess analytical methods. Adv. Sample Prep. 14, 100164 (2025).","journal-title":"Adv. Sample Prep."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39426-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39426-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39426-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:12:08Z","timestamp":1781637128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39426-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["39426"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-39426-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"1 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8263"}}