{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:40:11Z","timestamp":1792586411777,"version":"4.5.0"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Rilmazafone is a pro-drug that can be prescribed in Japan to treat insomnia. Rilmazafone metabolizes into active compounds by a ring closure resulting in a triazolo benzodiazepine structure similar to alprazolam. In mid-2022, the National Board of Forensic Medicine in Sweden were requested to investigate two separate deaths with the suspected use of pagoclone. Packages labeled \u201cPagoclone\u201d were found at each scene that was suspected to contain rilmazafone based on website information. During screening by high resolution mass spectrometry, rilmazafone metabolites were presumptively identified. Due to the lack of reference material for the active metabolites, the metabolites were synthesized in house and quantification of the compounds identified in the two autopsy cases was prompted. In Case 1, femoral blood concentrations of 7.9, 65 and 170 ng\/g of the metabolites rilmazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included the medications haloperidol, alimemazine, fluoxetine, olanzapine and acetaminophen. In Case 2, femoral blood concentrations of 1.7, 1.4 and 70 ng\/g of rimazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included loperamide, alimemazine and pregabalin. The intake of rilmazafone was determined as the cause of death in Case 1 and contributed in the Case 2.<\/jats:p>","DOI":"10.1093\/jat\/bkad041","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T22:42:50Z","timestamp":1687473770000},"page":"640-643","source":"Crossref","is-referenced-by-count":7,"title":["Rilmazafone: A designer benzodiazepine pro-drug involved in\u00a0fatal intoxications"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4222-9597","authenticated-orcid":false,"given":"Robert","family":"Kronstrand","sequence":"first","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, Link\u00f6ping 587 58, Sweden"},{"name":"Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University , Link\u00f6ping 581 83, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, Link\u00f6ping 587 58, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, Link\u00f6ping 587 58, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of physics, chemistry and biology, Link\u00f6ping university , Link\u00f6ping 581 83, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, Link\u00f6ping 587 58, Sweden"},{"name":"Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University , Link\u00f6ping 581 83, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-5379","authenticated-orcid":false,"given":"Michael T","family":"Truver","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine , 4800 SW 35th Drive, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"2023091515445666900_R1","article-title":"EMCDDA New benzodiazepines in\u00a0Europe\u2014a review","author":"European Monitoring Centre for Drugs and Drug Addiction"},{"key":"2023091515445666900_R2","article-title":"EMCDDA New psychoactive substances: 25 years of\u00a0early warning and\u00a0response in\u00a0Europe","author":"European Monitoring Centre for Drugs and Drug Addiction"},{"key":"2023091515445666900_R3","article-title":"NPS Benzodiazepines in\u00a0the United States\u2014Trend Report\u2014Q4 2022","author":"NPS Discovery"},{"key":"2023091515445666900_R4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40801-022-00306-6","article-title":"Itraconazole contaminated with rilmazafone in\u00a0Japan: a retrospective analysis using the Japanese Adverse Drug Event Report Database","volume":"9","author":"Tsuchiya","year":"2022","journal-title":"Drugs\u2014Real World Outcomes"},{"key":"2023091515445666900_R5","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/0006-2952(84)90287-9","article-title":"Detection and\u00a0determination of\u00a0active metabolites of\u00a01-(2-o-chlorobenzoyl-4-chlorophenyl)-5-glycyl-aminomethyl-3-dimethylcarbamoyl-1H-1,2,4-triazole hydrochloride dihydrate, (450191-S), in\u00a0rat tissues, using a radioreceptor assay for\u00a0benzodiazepines","volume":"33","author":"Fujimoto","year":"1984","journal-title":"Biochemical Pharmacology"},{"key":"2023091515445666900_R6","article-title":"MEDSAFE Classification of\u00a0Rilmazafone: Submission to the Medicines Classification Committee"},{"key":"2023091515445666900_R7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1254\/fpj.90.239","article-title":"Pharmacology of\u00a0a new sleep-inducer, 1H-1, 2, 4-triazolyl benzophenone derivative, 450191-S (VIII)","volume":"90","author":"Yamaguchi","year":"1987","journal-title":"Folia Pharmacologica Japonica"},{"key":"2023091515445666900_R8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1254\/fpj.84.25","article-title":"Pharmacology of\u00a0a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (II)","volume":"84","author":"Yamamoto","year":"1984","journal-title":"Folia Pharmacologica Japonica"},{"key":"2023091515445666900_R9","article-title":"Research Chemicals"},{"key":"2023091515445666900_R10","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1007\/s00216-013-6798-0","article-title":"Liquid chromatography\/time-of-flight mass spectrometry analysis of\u00a0postmortem blood samples for\u00a0targeted toxicological screening","volume":"405","author":"Roman","year":"2013","journal-title":"Analytical and Bioanalytical Chemistry"}],"container-title":["Journal of Analytical 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