title: Detection of main metabolites of XLR-11 and its thermal degradation product in human hepatoma HepaRG cells and human urine.
abstract: The metabolism of (1-(5-fluoropentyl)-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11), a novel synthetic cannabinoid, was studied using a HepaRG cell culture. The HepaRG cells were incubated with the drug for 48 hours and the metabolites were extracted from the culture medium by liquid-liquid extraction. The extract was analyzed by liquid chromatography/mass spectrometry to detect the metabolites. N-(5-Hydroxypentyl) metabolite and N-pentanoic acid metabolite were identified in the culture medium of XLR-11, and several other metabolites, presumably formed by oxidation of the first two metabolites and XLR-11, were detected. The extract of an XLR-11 user's urine was also analyzed; however, the metabolites detected in the urine were different from XLR-11 metabolites in the medium. A metabolic experiment with the thermal degradation product of XLR-11, XLR-11 degradant, using HepaRG cells revealed that the urinary metabolites were almost identical to the XLR-11 degradant metabolites. These findings suggest that most of the XLR-11 was degraded by heating when the user smoked the herbal product containing XLR-11.
authors.affiliation: National Research Institute of Police Science, First Chemistry Section, 6-3-1, Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kanamori
authors.forename: Koji
authors.initials: K
authors.lastname: Kanda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamuro
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsujikawa
authors.forename: Yuko Togawa
authors.initials: YT
authors.lastname: Iwata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
mesh_terms: D002186:Cannabinoids / Q000378:metabolism* / Q000652:urine*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D055030:Drug Users; D008401:Gas Chromatography-Mass Spectrometry; D006358:Hot Temperature; D006801:Humans; D059625:Liquid-Liquid Extraction; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D002186:Cannabinoids; C585106:XLR-11
keywords: hepatocyte; metabolism; synthetic cannabinoid; urine