title: Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue.
abstract: The data are reported for an in vitro metabolism study of two novel synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and its fluorinated analog N-(1-adamantyl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (5F-APICA, STS-135), which are active ingredients of smoking mixtures sold in Russia since 2012. The cannabinoids were isolated from herbal mixtures using preparative liquid chromatography and then incubated with human liver microsomes (HLMs). The formed metabolites were characterized by liquid chromatography - triple quadrupole mass spectrometry and high-resolution mass spectrometry with electrospray ionization in positive ion mode. It was found that HLMs produce mono-, di-, and trihydroxylated metabolites, as well as N-desalkyl metabolites, which can be further hydroxylated; the amide bond resisted the metabolic cleavage. For 5F-APICA, a series of oxidative defluorination products formed as well. For in vivo confirmation of the formed in vitro metabolites, spot urine samples from drug users were analyzed with the created method. It was shown that for the detection of APICA abuse, the preferred metabolites are the di- and tri-hydroxylated species, while in case of 5F-APICA, a monohydroxy metabolite is a better target. The N-despentyl (desfluoropentyl) hydroxyadamantyl metabolite also provides good retrospectivity to confirm the administration of any of these cannabinoids.
authors.affiliation: Moscow Antidoping Centre, 105005, Moscow, Elizavetinsky per. 10, Russia.
authors.forename: Tim
authors.initials: T
authors.lastname: Sobolevsky
authors.forename: Ilya
authors.initials: I
authors.lastname: Prasolov
authors.forename: Grigory
authors.initials: G
authors.lastname: Rodchenkov
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000652:urine; D002186:Cannabinoids / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D054879:Halogenation; D006801:Humans; D013287:Illicit Drugs / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D007211:Indoles / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D008862:Microsomes, Liver / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D002186:Cannabinoids; D013287:Illicit Drugs; D007211:Indoles; C584513:N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide; D000218:Adamantane
keywords: 5F-APICA; APICA; STS-135; anti-doping analysis; synthetic cannabinoids