Citation

Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O. Drug Test. Anal. 2018; 10(2): 365-371.

Affiliation

Department of Legal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Copyright

(Copyright © 2018, John Wiley and Sons)

DOI

10.1002/dta.2220

PMID

28560823

Abstract

An autopsy case in which the cause of death was judged as drug poisoning by two synthetic cannabinoids, including MAB-CHMINACA, was experienced. Although unchanged MAB-CHMINACA could be detected from solid tissues, blood and stomach contents in the case, the compound could not be detected from the urine specimen. In this article, we obtained six kinds of reference standards of MAB-CHMINACA metabolites from a commercial source. The MAB-CHMINACA metabolites from the urine specimen of the abuser were extracted by a QuEChERS method including dispersive solid-phase extraction, and analyzed by liquid chromatography-tandem mass spectrometry with or without hydrolysis with β-glucuronidase. Among the six MAB-CHMINACA metabolites tested, 2 predominant metabolites could be identified and quantified in the urine specimen of the deceased. After hydrolysis with β-glucuronidase, increase of the two metabolites was not observed. The metabolites detected were a 4-monohydroxycyclohexylmethyl metabolite M1 (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-((4-hydroxycyclohexyl)methyl)-1H-indazole-3-carbo-xamide) of MAB-CHMINACA, and a dihydroxyl (4-hydroxycyclohexylmethyl and tert-butyl hydroxyl) metabolite M11 (N-(1-amino-4-hydroxy-3,3-dimethyl-1-oxobutan-2-yl)-1-((4-hydroxycyclohexyl)methyl)-1H-indaz-ole-3-carboxamide). Their concentrations were 2.17±0.15 and 10.2±0.3 ng/mL (n = 3, each) for M1 and M11, respectively. Although there is one preceding in vitro study showing the estimation of metabolism of MAB-CHMINACA using human hepatocytes, this is the first report dealing with in vivo identification and quantification of MAB-CHMINACA metabolites in an authentic human urine specimen.

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Language: en

Keywords

4-Hydroxycyclohexylmethyl MAB-CHMINACA; In vivo human metabolism; LC-MS/MS; MAB-CHMINACA metabolites in human urine; tert-Butyl-hydroxyl MAB-CHMINACA