Doi Takahiro, Asada Akiko, Takeda Akihiro, Tagami Takaomi, Katagi Munehiro, Kamata Hiroe, Sawabe Yoshiyuki
Department of Food, Drugs and Environment, Osaka Prefectural Institute of Public Health, 1-3-69 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
Department of Food, Drugs and Environment, Osaka Prefectural Institute of Public Health, 1-3-69 Nakamichi, Higashinari-ku, Osaka 537-0025, Japan.
J Chromatogr A. 2016 Nov 18;1473:83-89. doi: 10.1016/j.chroma.2016.10.049. Epub 2016 Oct 19.
Synthetic cannabinoids, recently used as alternatives to Cannabis sativa, are among the most frequently abused drugs. Identified in 2014, the synthetic cannabinoids N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide (5F-AB-PINACA) and methyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]-valinate (5F-AMB) are carboxamides composed of 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid and valine amide/methyl ester. Because of their composition, these molecules have pairs of enantiomers derived from the chiral center of their amino acid structures. Previous studies on the identification of 5F-AB-PINACA and 5F-AMB did not consider the existence of enantiomers, and there have been no reports on the enantiopurities of synthetic cannabinoids. We synthesized both enantiomers of these compounds and then separated the enantiomers by liquid chromatography-high-resolution mass spectrometry using a column with a chiral stationary phase consisted with amylose tris (3-chloro-4-methylphenylcarbamate). Under the optimized conditions, the enantiomer resolutions were 2.2 and 2.3 for 5F-AB-PINACA and 5F-AMB, respectively. Analysis of 10 herbal samples containing 5F-AB-PINACA and one herbal sample containing 5F-AMB showed that they all contained the (S)-enantiomer, but the (R)-enantiomer was only detected in two samples and at a ratio of less than 20%.
合成大麻素是近年来被用作大麻替代品的最常被滥用的药物之一。2014年鉴定出的合成大麻素N-(1-氨基-3-甲基-1-氧代丁烷-2-基)-1-(5-氟戊基)-1H-吲唑-3-甲酰胺（5F-AB-PINACA）和甲基[1-(5-氟戊基)-1H-吲唑-3-羰基]-缬氨酸酯（5F-AMB）是由1-(5-氟戊基)-1H-吲唑-3-羧酸和缬氨酰胺/甲酯组成的羧酰胺。由于其组成，这些分子具有源自其氨基酸结构手性中心的对映异构体对。先前关于5F-AB-PINACA和5F-AMB鉴定的研究没有考虑对映异构体的存在，并且也没有关于合成大麻素对映体纯度的报道。我们合成了这些化合物的两种对映体，然后使用涂覆直链淀粉三(3-氯-4-甲基苯基氨基甲酸酯)手性固定相的柱，通过液相色谱-高分辨率质谱法分离对映体。在优化条件下，5F-AB-PINACA和5F-AMB的对映体分离度分别为2.2和2.3。对10个含有5F-AB-PINACA的草药样品和1个含有5F-AMB的草药样品分析表明，它们均含有(S)-对映体，但仅在两个样品中检测到(R)-对映体且比例低于20%。
