Watanabe Shimpei, Kuzhiumparambil Unnikrishnan, Winiarski Zofia, Fu Shanlin
Centre for Forensic Science, School of Mathematical and Physical Sciences, University of Technology Sydney (UTS), PO Box 123, Broadway, NSW 2007, Australia.
Centre for Forensic Science, School of Mathematical and Physical Sciences, University of Technology Sydney (UTS), PO Box 123, Broadway, NSW 2007, Australia; Plant Functional Biology and Climate Change Cluster, University of Technology Sydney (UTS), PO Box 123, Broadway, NSW 2007, Australia.
Forensic Sci Int. 2016 Apr;261:33-42. doi: 10.1016/j.forsciint.2015.12.023. Epub 2015 Dec 21.
Being marketed as "legal" smoking blends or mixtures, synthetic cannabinoids are abused widely owing to its cannabis-like effect. Due to the rapid introduction of new generation analogues of synthetic cannabinoids to escape from legislative/judicial control, the investigation of the metabolic pathways of these substances is of particular importance for drug control, abstinence and forensic toxicology purposes. In this study, the in vitro metabolism of JWH-018, JWH-073 and AM2201 by the fungus Cunninghamella elagans has been investigated with the purpose of validating its potential as a complementary model for investigating synthetic cannabinoid metabolism. JWH-018, JWH-073 and AM2201 were incubated for 72h with C. elegans. Detection of metabolites was based on liquid chromatography-tandem mass spectrometry and high resolution mass spectrometry analysis. C. elegans was found capable of producing the majority of the phase I metabolites observed in earlier in vitro and in vivo mammalian studies as a result of monohydroxylation, dihydroxylation, carboxylation, dehydrogenation, ketone formation, dihydrodiol formation, dihydrodiol formation with N-dealkylation and combinations thereof. C. elegans can thus be a useful and economic model for studying synthetic cannabinoid metabolism.
合成大麻素作为“合法”吸烟混合物或混合剂进行销售，因其具有类似大麻的效果而被广泛滥用。由于新一代合成大麻素类似物迅速出现以逃避立法/司法管控，因此对于药物管制、戒毒和法医毒理学目的而言，研究这些物质的代谢途径尤为重要。在本研究中，对雅致小克银汉霉对JWH - 018、JWH - 073和AM2201的体外代谢进行了研究，目的是验证其作为研究合成大麻素代谢的补充模型的潜力。将JWH - 018、JWH - 073和AM2201与雅致小克银汉霉一起孵育72小时。代谢物的检测基于液相色谱 - 串联质谱和高分辨率质谱分析。结果发现，雅致小克银汉霉能够产生早期体外和体内哺乳动物研究中观察到的大多数I相代谢物，这些代谢物是通过单羟基化、二羟基化、羧化、脱氢、酮形成、二氢二醇形成、伴有N - 脱烷基化的二氢二醇形成及其组合产生的。因此，雅致小克银汉霉可以成为研究合成大麻素代谢的有用且经济的模型。
