{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:08:59Z","timestamp":1775714939930,"version":"3.50.1"},"reference-count":26,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ISCIII, Fondo de Investigaci\u00f3n en Salud (FIS)-Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI17\/01962"],"award-info":[{"award-number":["PI17\/01962"]}]},{"name":"ISCIII, Fondo de Investigaci\u00f3n en Salud (FIS)-Fondo Europeo de Desarrollo Regional (FEDER)","award":["PI20\/00879"],"award-info":[{"award-number":["PI20\/00879"]}]},{"name":"ISCIII, Fondo de Investigaci\u00f3n en Salud (FIS)-Fondo Europeo de Desarrollo Regional (FEDER)","award":["FI18\/00179"],"award-info":[{"award-number":["FI18\/00179"]}]},{"name":"ISCIII, Fondo de Investigaci\u00f3n en Salud (FIS)-Fondo Europeo de Desarrollo Regional (FEDER)","award":["PT20\/00018"],"award-info":[{"award-number":["PT20\/00018"]}]},{"name":"predoctoral PFIS fellowship","award":["PI17\/01962"],"award-info":[{"award-number":["PI17\/01962"]}]},{"name":"predoctoral PFIS fellowship","award":["PI20\/00879"],"award-info":[{"award-number":["PI20\/00879"]}]},{"name":"predoctoral PFIS fellowship","award":["FI18\/00179"],"award-info":[{"award-number":["FI18\/00179"]}]},{"name":"predoctoral PFIS fellowship","award":["PT20\/00018"],"award-info":[{"award-number":["PT20\/00018"]}]},{"name":"Plataformas ISCIII de apoyo a la I + D + I en Biomedicina y Ciencias de la Salud","award":["PI17\/01962"],"award-info":[{"award-number":["PI17\/01962"]}]},{"name":"Plataformas ISCIII de apoyo a la I + D + I en Biomedicina y Ciencias de la Salud","award":["PI20\/00879"],"award-info":[{"award-number":["PI20\/00879"]}]},{"name":"Plataformas ISCIII de apoyo a la I + D + I en Biomedicina y Ciencias de la Salud","award":["FI18\/00179"],"award-info":[{"award-number":["FI18\/00179"]}]},{"name":"Plataformas ISCIII de apoyo a la I + D + I en Biomedicina y Ciencias de la Salud","award":["PT20\/00018"],"award-info":[{"award-number":["PT20\/00018"]}]},{"name":"project \u201cImplementation of the identification and study of the effects of NPS: Development of a multicenter research to enhance the database of the National drug Addiction Observatory and the Early Warning System\u201d","award":["PI17\/01962"],"award-info":[{"award-number":["PI17\/01962"]}]},{"name":"project \u201cImplementation of the identification and study of the effects of NPS: Development of a multicenter research to enhance the database of the National drug Addiction Observatory and the Early Warning System\u201d","award":["PI20\/00879"],"award-info":[{"award-number":["PI20\/00879"]}]},{"name":"project \u201cImplementation of the identification and study of the effects of NPS: Development of a multicenter research to enhance the database of the National drug Addiction Observatory and the Early Warning System\u201d","award":["FI18\/00179"],"award-info":[{"award-number":["FI18\/00179"]}]},{"name":"project \u201cImplementation of the identification and study of the effects of NPS: Development of a multicenter research to enhance the database of the National drug Addiction Observatory and the Early Warning System\u201d","award":["PT20\/00018"],"award-info":[{"award-number":["PT20\/00018"]}]},{"name":"project \u201cNational Early Warning System on Drugs (SNAP)\u201d","award":["PI17\/01962"],"award-info":[{"award-number":["PI17\/01962"]}]},{"name":"project \u201cNational Early Warning System on Drugs (SNAP)\u201d","award":["PI20\/00879"],"award-info":[{"award-number":["PI20\/00879"]}]},{"name":"project \u201cNational Early Warning System on Drugs (SNAP)\u201d","award":["FI18\/00179"],"award-info":[{"award-number":["FI18\/00179"]}]},{"name":"project \u201cNational Early Warning System on Drugs (SNAP)\u201d","award":["PT20\/00018"],"award-info":[{"award-number":["PT20\/00018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50\u2013200 mg methylone to 12 male volunteers. A new LC-MS\/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 \u00b5L of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 \u00b5L of plasma. Two mL of chloroform and ethyl acetate 9:1 (v\/v) were then added, mixed well and centrifuged. The supernatant was fortified with 0.1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS\/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng\/mL, AUC0\u201324 values were reported as 1042.8, 2441.2, 3524.4 and 5067.9 h\u00b7ng\/mL and T1\/2 values as 5.8, 6.4, 6.9 and 6.4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1.5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10\u201314-fold lower and an AUC0\u201324 value that was 21\u201329-fold lower. Methylone pharmacokinetics was linear across 50\u2013200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS\/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50\u2013200 mg.<\/jats:p>","DOI":"10.3390\/ijms232314636","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T01:46:56Z","timestamp":1669254416000},"page":"14636","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4641-8600","authenticated-orcid":false,"given":"Lourdes","family":"Poyatos","sequence":"first","affiliation":[{"name":"Servei de Farmacologia Cl\u00ednica, Hospital Universitari Germans Trias i Pujol (HUGTiP, IGTP), Universitat Aut\u00f2noma de Barcelona, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-5277","authenticated-orcid":false,"given":"Alfredo Fabrizio","family":"Lo Faro","sequence":"additional","affiliation":[{"name":"Department of Excellence-Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diletta","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Department of Excellence-Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Sprega","sequence":"additional","affiliation":[{"name":"Department of Excellence-Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Malaca","sequence":"additional","affiliation":[{"name":"Department of Excellence-Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Pichini","sequence":"additional","affiliation":[{"name":"National Centre on Addiction and Doping, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-4645","authenticated-orcid":false,"given":"Marilyn A.","family":"Huestis","sequence":"additional","affiliation":[{"name":"Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Papaseit","sequence":"additional","affiliation":[{"name":"Servei de Farmacologia Cl\u00ednica, Hospital Universitari Germans Trias i Pujol (HUGTiP, IGTP), Universitat Aut\u00f2noma de Barcelona, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-6918","authenticated-orcid":false,"given":"Clara","family":"P\u00e9rez-Ma\u00f1\u00e1","sequence":"additional","affiliation":[{"name":"Servei de Farmacologia Cl\u00ednica, Hospital Universitari Germans Trias i Pujol (HUGTiP, IGTP), Universitat Aut\u00f2noma de Barcelona, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Paolo","family":"Busard\u00f2","sequence":"additional","affiliation":[{"name":"Department of Excellence-Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8338-7543","authenticated-orcid":false,"given":"Mag\u00ed","family":"Farr\u00e9","sequence":"additional","affiliation":[{"name":"Servei de Farmacologia Cl\u00ednica, Hospital Universitari Germans Trias i Pujol (HUGTiP, IGTP), Universitat Aut\u00f2noma de Barcelona, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11419-017-0385-6","article-title":"The newest cathinone derivatives as designer drugs: An analytical and toxicological review","volume":"36","author":"Majchrzak","year":"2018","journal-title":"Forensic Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1007\/s00204-021-03083-3","article-title":"An updated review on synthetic cathinones","volume":"95","author":"Soares","year":"2021","journal-title":"Arch. 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Assur."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14636\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:25:30Z","timestamp":1760145930000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,23]]},"references-count":26,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314636"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314636","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,23]]}}}