{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:24:14Z","timestamp":1768883054073,"version":"3.49.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-14772-9","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T12:03:48Z","timestamp":1755691428000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Drug screening in pharmaceutical and forensic applications using extractive-liquid sampling electron ionization-mass spectrometry (E-LEI-MS)"],"prefix":"10.1038","volume":"15","author":[{"given":"Giovanna","family":"Nevola","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Arig\u00f2","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Famiglini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Renzoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Agostini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achille","family":"Cappiello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"14772_CR1","doi-asserted-by":"publisher","first-page":"6429","DOI":"10.1038\/s41598-023-33647-5","volume":"13","author":"A Arig\u00f2","year":"2013","unstructured":"Arig\u00f2, A. et al. Extractive\u2013liquid sampling electron ionization\u2013mass spectrometry (E\u2013LEI\u2013MS): A new powerful combination for direct analysis. Sci. Rep. 13, 6429. https:\/\/doi.org\/10.1038\/s41598-023-33647-5 (2013).","journal-title":"Sci. Rep."},{"key":"14772_CR2","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.talanta.2018.01.013","volume":"181","author":"J P\u0142otka-Wasylka","year":"2018","unstructured":"P\u0142otka-Wasylka, J. A new tool for the evaluation of the analytical procedure: Green analytical procedure index. Talanta 181, 204\u2013209. https:\/\/doi.org\/10.1016\/j.talanta.2018.01.013 (2018).","journal-title":"Talanta"},{"key":"14772_CR3","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1351\/PAC-REC-06-04-06","volume":"85","author":"KK Murray","year":"2013","unstructured":"Murray, K. K. et al. Definition of terms relating to mass spectrometry (IUPAC Recommendations). Pure Appl. Chem. 85, 1515\u20131609. https:\/\/doi.org\/10.1351\/PAC-REC-06-04-06 (2013).","journal-title":"Pure Appl. Chem."},{"key":"14772_CR4","doi-asserted-by":"publisher","first-page":"6471","DOI":"10.1126\/science.1104404","volume":"30","author":"Z Tak\u00e1ts","year":"2004","unstructured":"Tak\u00e1ts, Z., Wiseman, J. M., Gologan, B. & Cooks, R. G. Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 30, 6471\u20136473. https:\/\/doi.org\/10.1126\/science.1104404 (2004).","journal-title":"Science"},{"key":"14772_CR5","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1021\/ac050162j","volume":"77","author":"RB Cody","year":"2005","unstructured":"Cody, R. B., Laram\u00e9\u00e8, J. A. & Durst, H. D. Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal. Chem. 77, 2297\u20132302. https:\/\/doi.org\/10.1021\/ac050162j (2005).","journal-title":"Anal. Chem."},{"key":"14772_CR6","doi-asserted-by":"publisher","first-page":"49988","DOI":"10.1039\/C7AY00867H","volume":"34","author":"TP Forbes","year":"2017","unstructured":"Forbes, T. P., Sisco, E., Staymates, M. & Gillen, G. DART-MS analysis of inorganic explosives using high temperature thermal desorption. Anal. Method. 34, 49988\u201344996. https:\/\/doi.org\/10.1039\/C7AY00867H (2017).","journal-title":"Anal. Method"},{"key":"14772_CR7","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1007\/s00339-019-2564-2","volume":"125","author":"A Wojtowicz","year":"2019","unstructured":"Wojtowicz, A. & Wietecha-Poslunszny, R. DESI-MS analysis of human fluid and tissue for forensic applications. Appl. Phys. A. 125, 312. https:\/\/doi.org\/10.1007\/s00339-019-2564-2 (2019).","journal-title":"Appl. Phys. A"},{"key":"14772_CR8","doi-asserted-by":"publisher","first-page":"100294","DOI":"10.1016\/j.forc.2020.100294","volume":"22","author":"E Sisco","year":"2021","unstructured":"Sisco, E. & Forbes, T. P. Forensic applications of DART-MS: A review of recent literature. Forensic Chem. 22, 100294. https:\/\/doi.org\/10.1016\/j.forc.2020.100294 (2021).","journal-title":"Forensic Chem."},{"key":"14772_CR9","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/mas.21680","volume":"41","author":"C Harkin","year":"2021","unstructured":"Harkin, C. et al. On-tissue chemical derivatization in mass spectrometry imaging. Mass. Spec. Rev. 41, 645\u2013898. https:\/\/doi.org\/10.1002\/mas.21680 (2021).","journal-title":"Mass. Spec. Rev."},{"key":"14772_CR10","doi-asserted-by":"publisher","unstructured":"Cardoso-Palacios, C. & Lanekoff, I. Direct Analysis of Pharmaceutical Drugs Using Nano-DESI MS. J. Anal. Methods Chem., 3591908, (2016). https:\/\/doi.org\/10.1155\/2016\/3591908 (2016).","DOI":"10.1155\/2016\/3591908"},{"key":"14772_CR11","doi-asserted-by":"publisher","first-page":"4831","DOI":"10.1039\/D0AY01474E","volume":"12","author":"M Beneito-Cambra","year":"2020","unstructured":"Beneito-Cambra, M. et al. Ambient (desorption\/ionization) mass spectrometry methods for pesticide testing in food: A review. Anal. Methods. 12, 4831. https:\/\/doi.org\/10.1039\/D0AY01474E (2020).","journal-title":"Anal. Methods"},{"key":"14772_CR12","doi-asserted-by":"publisher","first-page":"117814","DOI":"10.1016\/j.trac.2024.117814","volume":"178","author":"Y Lv","year":"2024","unstructured":"Lv, Y., Zhao, J., Xue, H. & Ma, Q. Ambient ionization mass spectrometry for food analysis: recent progress and applications. TrAC 178, 117814. https:\/\/doi.org\/10.1016\/j.trac.2024.117814 (2024).","journal-title":"TrAC"},{"key":"14772_CR13","doi-asserted-by":"publisher","first-page":"9265","DOI":"10.1002\/rcm.9265","volume":"36","author":"L Mainero Rocca","year":"2022","unstructured":"Mainero Rocca, L., L\u2019Episcopo, N., Giordiani, A. & Staderini, A. Direct multiclass desorption electrospray ionization-tandem mass spectrometry method for the analysis of sleep inducers and ototoxic drug in dried blood spots. Rapid Commun. Mass. Spectrom. 36, 9265. https:\/\/doi.org\/10.1002\/rcm.9265 (2022).","journal-title":"Rapid Commun. Mass. Spectrom."},{"key":"14772_CR14","doi-asserted-by":"publisher","first-page":"340490","DOI":"10.1016\/j.aca.2022.340490","volume":"1233","author":"D Mesa Sanchez","year":"2022","unstructured":"Mesa Sanchez, D. et al. Mass spectrometry imaging of diclofenac and its metabolites in tissues using nanospray desorption electrospray ionization. Anal. Chim. Acta. 1233, 340490. https:\/\/doi.org\/10.1016\/j.aca.2022.340490 (2022).","journal-title":"Anal. Chim. Acta"},{"key":"14772_CR15","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1002\/mas.21736","volume":"42","author":"T Soudah","year":"2021","unstructured":"Soudah, T., Zoabi, A. & Margulis, K. Desorption electrospray ionization mass spectrometry imaging in discovery and development of novel therapies. Mass. Spectrom. Rev. 42, 751\u2013778. https:\/\/doi.org\/10.1002\/mas.21736 (2021).","journal-title":"Mass. Spectrom. Rev."},{"key":"14772_CR16","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1002\/cem.3412","volume":"36","author":"AJ Taylor","year":"2022","unstructured":"Taylor, A. J. et al. Classification of tablet formulation by desorption electrospray ionization mass spectrometry and transmission Raman spectroscopy. J. Chemometrics. 36, 3412. https:\/\/doi.org\/10.1002\/cem.3412 (2022).","journal-title":"J. Chemometrics"},{"key":"14772_CR17","doi-asserted-by":"publisher","first-page":"114720","DOI":"10.1016\/j.jpba.2022.114720","volume":"214","author":"D Monser","year":"2022","unstructured":"Monser, D. et al. Fast and semiquantitative screening for sildenafil in herbal over-the-counter formulations with atmospheric pressure solid analysis probe (ASAP) to prevent medicinal adulteration. J. Pharm. Biomed. Anal. 214, 114720. https:\/\/doi.org\/10.1016\/j.jpba.2022.114720 (2022).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"14772_CR18","doi-asserted-by":"publisher","first-page":"183","DOI":"10.26355\/eurrev_202201_27767","volume":"26","author":"K Skov","year":"2022","unstructured":"Skov, K., Johansen, S. S., Linnet, K. & Nielsen, M. K. K. A review on the forensic toxicology of global drug-facilitated sexual assaults. Eur. Rev. Med. Pharmacol. Sci. 26, 183\u2013197. https:\/\/doi.org\/10.26355\/eurrev_202201_27767 (2022).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"14772_CR19","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.jpha.2023.03.007","volume":"13","author":"Y Zhang","year":"2023","unstructured":"Zhang, Y. et al. Benzodiazepines in complex biological matrices: Recent updates on pretreatment and detection methods. J. Pharm. Anal. 13, 442\u2013462. https:\/\/doi.org\/10.1016\/j.jpha.2023.03.007 (2023).","journal-title":"J. Pharm. Anal."},{"key":"14772_CR20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s41935-022-00276-4","volume":"12","author":"S Gupta","year":"2022","unstructured":"Gupta, S. & Samal, N. Application of direct analysis in real-time mass spectrometry (DART-MS) in forensic science: A comprehensive review. Egypt. J. Forensic Sci. 12, 17. https:\/\/doi.org\/10.1186\/s41935-022-00276-4 (2022).","journal-title":"Egypt. J. Forensic Sci."},{"key":"14772_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jat\/bkac017","volume":"47","author":"M P\u00e9rez Orts","year":"2023","unstructured":"P\u00e9rez Orts, M., van Asten, A. & Kohler, I. The evolution toward designer benzodiazepines in Drug-Facilitated sexual assault cases. J. Anal. Toxicol. 47, 1\u201325. https:\/\/doi.org\/10.1093\/jat\/bkac017 (2023).","journal-title":"J. Anal. Toxicol."},{"key":"14772_CR22","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1002\/elps.201500517","volume":"37","author":"G Famiglini","year":"2016","unstructured":"Famiglini, G., Termopoli, V., Palma, P. & Cappiello, A. Liquid chromatography-electron ionization tandem mass spectrometry with the Direct-EI interface in the fast determination of diazepam and flunitrazepam in alcoholic beverages. Electrophoresis 37, 1048\u20131054. https:\/\/doi.org\/10.1002\/elps.201500517 (2016).","journal-title":"Electrophoresis"},{"key":"14772_CR23","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.scijus.2011.08.007","volume":"52","author":"P D\u2019Aloise","year":"2012","unstructured":"D\u2019Aloise, P. & Chen, H. Rapid determination of flunitrazepam in alcoholic beverages by desorption electrospray ionization-mass spectrometry. Sci. Justice. 52, 2\u20138. https:\/\/doi.org\/10.1016\/j.scijus.2011.08.007 (2012).","journal-title":"Sci. Justice"},{"key":"14772_CR24","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1002\/mas.20054","volume":"24","author":"A Cappiello","year":"2005","unstructured":"Cappiello, A., Famiglini, G., Palma, P. & Siviero, A. Liquid Chromatography-Electron ionization mass spectrometry: Fields of application and evaluation of the performance of a Direct-EI interface. Mass. Spectrom. Rev. 24, 978\u2013989. https:\/\/doi.org\/10.1002\/mas.20054 (2005).","journal-title":"Mass. Spectrom. Rev."},{"key":"14772_CR25","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1021\/acs.analchem.6b04646","volume":"89","author":"V Termpoli","year":"2017","unstructured":"Termpoli, V., Famiglini, G., Palma, P., Piergiovanni, M. & Cappiello, A. Atmospheric pressure vaporization mechanism for coupling a liquid phase with electron ionization mass spectrometry. Anal. Chem. 89, 2049\u20132056. https:\/\/doi.org\/10.1021\/acs.analchem.6b04646 (2017).","journal-title":"Anal. Chem."},{"key":"14772_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10408347.2024.2381543","volume":"24","author":"G Grasselli","year":"2024","unstructured":"Grasselli, G., Arig\u00f2, A., Palma, P., Famiglini, G. & Cappiello, A. Latest developments in direct and Non-Direct LC-MS methods based on liquid electron ionization (LEI). Crit. Rev. Anal. Chem. 24, 1\u201318. https:\/\/doi.org\/10.1080\/10408347.2024.2381543 (2024).","journal-title":"Crit. Rev. Anal. Chem."},{"key":"14772_CR27","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.jchromb.2005.02.015","volume":"819","author":"F Meng","year":"2005","unstructured":"Meng, F., Chen, X., Zeng, Y. & Zhong, D. Sensitive liquid chromatography-tandem mass spectrometry method for the determination of cefixime in human plasma: Application to a Pharmacokinetic study. J. Chromatogr. B. 819, 277\u2013282. https:\/\/doi.org\/10.1016\/j.jchromb.2005.02.015 (2005).","journal-title":"J. Chromatogr. B"},{"key":"14772_CR28","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.jpha.2014.10.005","volume":"5","author":"B Yilmaz","year":"2015","unstructured":"Yilmaz, B. & Ciltas, U. Determination of diclofenac in pharmaceutical preparations by voltammetry and gas chromatography methods. J. Pharm. Anal. 5, 153\u2013160. https:\/\/doi.org\/10.1016\/j.jpha.2014.10.005 (2015).","journal-title":"J. Pharm. Anal."},{"key":"14772_CR29","doi-asserted-by":"publisher","unstructured":"Merone, G. M. et al. Fast Quantitative LC-MS\/MS Determination of Illicit Substances in Solid and Liquid Unknown Seized Sample. Anal. Chem., 93, 16308\u201316313, (2021). https:\/\/doi.org\/10.1021\/acs.analchem.1c03310","DOI":"10.1021\/acs.analchem.1c03310"},{"key":"14772_CR30","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.forsciint.2018.08.034","volume":"292","author":"A Grela","year":"2018","unstructured":"Grela, A., Gautam, L. & Cole, M. D. A multifactorial critical appraisal of substances found in drug facilitated sexual assault cases. Forensic Sci. Int. 292, 50\u201360. https:\/\/doi.org\/10.1016\/j.forsciint.2018.08.034 (2018).","journal-title":"Forensic Sci. Int."},{"key":"14772_CR31","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1021\/acs.analchem.0c04663","volume":"93","author":"M Locatelli","year":"2021","unstructured":"Locatelli, M. et al. Fabric-Phase sorptive membrane array as a noninvasive in vivo sampling device for human exposure to different compounds. Anal. Chem. 93, 1957\u20131961. https:\/\/doi.org\/10.1021\/acs.analchem.0c04663 (2021).","journal-title":"Anal. Chem."},{"key":"14772_CR32","doi-asserted-by":"publisher","first-page":"100068","DOI":"10.1016\/j.sampre.2023.100068","volume":"6","author":"M Locatelli","year":"2023","unstructured":"Locatelli, M. et al. Green profile tools: Current status and future perspectives. Adv. Sample Prep. 6, 100068. https:\/\/doi.org\/10.1016\/j.sampre.2023.100068 (2023).","journal-title":"Adv. Sample Prep"},{"key":"14772_CR33","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-Analytical greenness metric approach and software. Anal. Chem. 92, 14, 10076\u201310082. https:\/\/doi.org\/10.1021\/acs.analchem.0c01887 (2020).","journal-title":"Anal. Chem."},{"key":"14772_CR34","doi-asserted-by":"publisher","unstructured":"Monsour, F. R., Plotka-Wasylka, J., Locatelli, M. & Modified, G. A. P. I. (eds) (MoGAPI) Tool and Software for the Assessment of Method Greenness: Case Studies and Applications. Analytica 5, 451\u2013457, (2024). https:\/\/doi.org\/10.3390\/analytica5030030.","DOI":"10.3390\/analytica5030030"},{"key":"14772_CR35","doi-asserted-by":"publisher","unstructured":"Monsour, 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 https:\/\/doi.org\/10.1016\/j.sampre.2025.100164 (2025).","DOI":"10.1016\/j.sampre.2025.100164"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14772-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14772-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14772-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T12:03:49Z","timestamp":1755691429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-14772-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["14772"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-14772-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]},"assertion":[{"value":"7 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"30578"}}