Rilmazafone: A Designer Benzodiazepine Pro-Drug Involved in Fatal Intoxications

Kronstrand, Robert,1966-Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden (författare)

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 "Pagoclone" 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.

Roman, MarkusNatl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden (författare)
Johansson, AnnaNatl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden (författare)
Wu, Xiongyu,1972-Linköpings universitet,Kemi,Tekniska fakulteten(Swepub:liu)xiowu62 (författare)
Gréen, Henrik,1975-Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Artillerigatan 12, S-58758 Linkoping, Sweden(Swepub:liu)hengr89 (författare)
Truver, Michael T.Univ Florida, FL 32610 USA (författare)
Linköpings universitetAvdelningen för klinisk kemi och farmakologi (creator_code:org_t)

Ingår i:Journal of Analytical Toxicology: OXFORD UNIV PRESS INC47:7, s. 640-6430146-47601945-2403

Av författaren/redakt...: Kronstrand, Robe ...; Roman, Markus; Johansson, Anna; Wu, Xiongyu, 197 ...; Gréen, Henrik, 1 ...; Truver, Michael ...

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