Kanamori Tatsuyuki, Kanda Koji, Yamamuro Tadashi, Kuwayama Kenji, Tsujikawa Kenji, Iwata Yuko Togawa, Inoue Hiroyuki
National Research Institute of Police Science, First Chemistry Section, 6-3-1, Kashiwanoha, Kashiwa, Chiba, 277-0882, Japan.
Drug Test Anal. 2015 Apr;7(4):341-5. doi: 10.1002/dta.1765. Epub 2015 Jan 19.
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.
使用HepaRG细胞培养研究了新型合成大麻素（1-（5-氟戊基）-1H-吲哚-3-基）（2,2,3,3-四甲基环丙基）甲酮（XLR-11）的代谢情况。将HepaRG细胞与该药物孵育48小时，然后通过液-液萃取从培养基中提取代谢物。通过液相色谱/质谱分析提取物以检测代谢物。在XLR-11的培养基中鉴定出N-（5-羟基戊基）代谢物和N-戊酸代谢物，并且检测到了其他几种代谢物，推测是由前两种代谢物和XLR-11氧化形成的。还分析了一名XLR-11使用者尿液的提取物；然而，尿液中检测到的代谢物与培养基中的XLR-11代谢物不同。使用HepaRG细胞对XLR-11的热降解产物XLR-11降解物进行的代谢实验表明，尿液代谢物与XLR-11降解物代谢物几乎相同。这些发现表明，当使用者吸食含有XLR-11的草药产品时，大部分XLR-11会因加热而降解。
