{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T02:12:24Z","timestamp":1770516744773,"version":"3.49.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"The Intramural Research Program (IRP) of the National Institute on Drug Abuse"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>In 2014, 2 novel synthetic cannabinoids, MN-18 and its 5-fluoro analog, 5F-MN-18, were first identified in an ongoing survey of novel psychoactive substances in Japan. In vitro pharmacological assays revealed that MN-18 and 5F-MN-18 displayed high binding affinities to human CB1 and CB2 receptors, with Ki being 1.65\u20133.86 nmol\/L. MN-18 and 5F-MN-18 were scheduled in Japan and some other countries in 2014. Despite increasing prevalence, no human metabolism data are currently available, making it challenging for forensic laboratories to confirm intake of MN-18 or 5F-MN-18.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We incubated 10 \u03bcmol\/L of MN-18 and 5F-MN-18 in human hepatocytes for 3 h and analyzed the samples on a TripleTOF 5600+ high-resolution mass spectrometer to identify appropriate marker metabolites. Data were acquired via full scan and information-dependent acquisition-triggered product ion scans with mass defect filter.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In total, 13 MN-18 metabolites were detected, with the top 3 abundant metabolites being 1-pentyl-1H-indazole-3-carboxylic acid, pentyl-carbonylated MN-18, and naphthalene-hydroxylated MN-18. For 5F-MN-18, 20 metabolites were observed, with the top 3 abundant metabolites being 5\u2032-OH-MN-18, MN-18 pentanoic acid, and 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>We have characterized MN-18 and 5F-MN-18 metabolism with human hepatocytes and high-resolution mass spectrometry, and we recommend characteristic major metabolites for clinical and forensic laboratories to identify MN-18 and 5F-MN-18 intake and link observed adverse events to these novel synthetic cannabinoids.<\/jats:p><\/jats:sec>","DOI":"10.1373\/clinchem.2017.277152","type":"journal-article","created":{"date-parts":[[2017,8,19]],"date-time":"2017-08-19T00:55:16Z","timestamp":1503104116000},"page":"1753-1763","source":"Crossref","is-referenced-by-count":12,"title":["Human Hepatocyte Metabolism of Novel Synthetic Cannabinoids MN-18 and Its 5-Fluoro Analog 5F-MN-18"],"prefix":"10.1093","volume":"63","author":[{"given":"Xingxing","family":"Diao","sequence":"first","affiliation":[{"name":"Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Carlier","sequence":"first","affiliation":[{"name":"Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingshe","family":"Zhu","sequence":"first","affiliation":[{"name":"MassDefect Technologies, Princeton, NJ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilyn A","family":"Huestis","sequence":"first","affiliation":[{"name":"Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD"},{"name":"University of Maryland School of Medicine, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"2020022606152756200_B1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.drugalcdep.2014.08.005","article-title":"Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications","volume":"144","author":"Castaneto","year":"2014","journal-title":"Drug Alcohol Depend"},{"key":"2020022606152756200_B2","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11419-015-0287-4","article-title":"4-Methoxy-alpha-PVP: in silico prediction, metabolic stability, and metabolite identification by human hepatocyte incubation and high-resolution mass spectrometry","volume":"34","author":"Ellefsen","year":"2016","journal-title":"Forensic Toxicol"},{"key":"2020022606152756200_B3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pnpbp.2012.04.017","article-title":"Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids","volume":"39","author":"Seely","year":"2012","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2020022606152756200_B4","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1208\/s12248-016-9867-4","article-title":"In vitro and in vivo human metabolism of synthetic cannabinoids FDU-PB-22 and FUB-PB-22","volume":"18","author":"Diao","year":"2016","journal-title":"AAPS J"},{"key":"2020022606152756200_B5","first-page":"242","article-title":"Postmortem and toxicological findings in a series of furanylfentanyl-related deaths","volume":"41","author":"Guerrieri","year":"2017","journal-title":"J Anal Toxicol"},{"key":"2020022606152756200_B6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1373\/clinchem.2015.248096","article-title":"Putting designer drugs back in Pandora's box: analytical challenges and metabolite identification","volume":"62","author":"Vikingsson","year":"2016","journal-title":"Clin Chem"},{"key":"2020022606152756200_B7","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4155\/bio.15.237","article-title":"In vitro, in vivo and in silico metabolic profiling of alpha-pyrrolidinopentiothiophenone, a novel thiophene stimulant","volume":"8","author":"Swortwood","year":"2016","journal-title":"Bioanalysis"},{"key":"2020022606152756200_B8","first-page":"1","article-title":"Adverse events associated with the use of synthetic cannabinoids\u2014Mississippi, 2015","volume":"31","author":"Mississippi State Department of Health","year":"2015","journal-title":"Mississippi Morb Rep"},{"key":"2020022606152756200_B9","unstructured":"New York City Department of Health and Mental Hygiene. 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