Phase I metabolism of the carbazole-derived synthetic cannabinoids EG-018, EG-2201, and MDMB-CHMCZCA and detection in human urine samples.
Synthetic cannabinoids (SCs) are a structurally diverse class of new psychoactive substances. Most SCs used for recreational purposes are based on indole or indazole core structures. EG-018 (naphthalen-1-yl(9-pentyl-9H-carbazol-3-yl)methanone), EG-2201 ((9-(5-fluoropentyl)-9H-carbazol-3-yl)(naphthalen-1-yl)methanone), and MDMB-CHMCZCA (methyl 2-(9-(cyclohexylmethyl)-9H-carbazole-3-carboxamido)-3,3-dimethylbutanoate) are 3 representatives of a structural subclass of SCs, characterized by a carbazole core system. In vitro and in vivo phase I metabolism studies were conducted to identify the most suitable metabolites for the detection of these substances in urine screening. Detection and characterization of metabolites were performed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (LC-ESI-QToF-MS). Eleven in vivo metabolites were detected in urine samples positive for metabolites of EG-018 (n = 8). A hydroxypentyl metabolite, most probably the 4-hydroxypentyl isomer, and an N-dealkylated metabolite mono-hydroxylated at the carbazole core system were most abundant. In vitro studies of EG-018 and EG-2201 indicated that oxidative defluorination of the 5-fluoropentyl side chain of EG-2201 as well as dealkylation led to common metabolites with EG-018. This has to be taken into account for interpretation of analytical findings. A differentiation between EG-018 and EG-2201 (n = 1) uptake is possible by the detection of compound-specific in vivo phase I metabolites evaluated in this study. Out of 30 metabolites detected in urine samples of MDMB-CHMCZCA users (n = 20), a metabolite mono-hydroxylated at the cyclohexyl methyl tail is considered the most suitable compound-specific consumption marker while a biotransformation product of mono-hydroxylation in combination with hydrolysis of the terminal methyl ester function provides best sensitivity due to its high abundance.
['Mogler|Lukas|L|http://orcid.org/0000-0001-8987-2785', 'Franz|Florian|F|http://orcid.org/0000-0001-6158-2882', 'Wilde|Maurice|M|', 'Huppertz|Laura M|LM|', 'Halter|Sebastian|S|', 'Angerer|Verena|V|', 'Moosmann|Bjoern|B|http://orcid.org/0000-0003-1757-6359', 'Auwärter|Volker|V|http://orcid.org/0000-0002-1883-2804']
D001711:Biotransformation D002186:Cannabinoids D002227:Carbazoles D002851:Chromatography, High Pressure Liquid D006801:Humans D013287:Illicit Drugs D007202:Indicators and Reagents D008862:Microsomes, Liver D021241:Spectrometry, Mass, Electrospray Ionization D015813:Substance Abuse Detection D053719:Tandem Mass Spectrometry
metabolism synthetic cannabinoid new psychoactive substances consumption marker carbazole derivative