Phase I metabolism of the recently emerged synthetic cannabinoid CUMYL-PEGACLONE and detection in human urine samples.
Indole-, indazole-, or azaindole-based synthetic cannabinoids (SCs), bearing a cumyl substituent are a widespread, recreationally used subgroup of new psychoactive substances (NPS). The latest cumyl-derivative, CUMYL-PEGACLONE, emerged in December 2016 on the German drug market. The substance features a novel γ-carboline core structure, which is most likely synthesized to bypass generic legislative approaches to control SCs by prohibiting distinct core structures. Using liquid chromatography-tandem mass spectrometry and liquid chromatography-high resolution mass spectrometry techniques, the main in vivo phase I metabolites of this new substance were detected. A pooled human liver microsome assay was applied to generate in vitro reference spectra of CUMYL-PEGACLONE phase I metabolites. Additionally, 30 urine samples were investigated leading to 22 in vivo metabolites. A metabolite mono-hydroxylated at the γ-carbolinone core system and a metabolite with an additional carbonyl group at the pentyl side chain were evaluated as highly specific and sensitive markers to proof CUMYL-PEGACLONE uptake. Moreover, 3 immunochemical assays commonly used for SC screening in urine were tested for their capability of detecting the new drug but failed due to insufficient cross-reactivity.
['Mogler|Lukas|L|http://orcid.org/0000-0001-8987-2785', 'Wilde|Maurice|M|', 'Huppertz|Laura M|LM|', 'Weinfurtner|Georg|G|', 'Franz|Florian|F|http://orcid.org/0000-0001-6158-2882', 'Auwärter|Volker|V|http://orcid.org/0000-0002-1883-2804']
D002186:Cannabinoids D002851:Chromatography, High Pressure Liquid D015198:Designer Drugs D006801:Humans D013287:Illicit Drugs D007211:Indoles D008862:Microsomes, Liver D011619:Psychotropic Drugs D021241:Spectrometry, Mass, Electrospray Ionization D015813:Substance Abuse Detection
new psychoactive substances metabolites γ-carbolinone designer drugs proof of consumption