Tentative identification of the metabolites of (1-(cyclohexylmethyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone, and the product of its thermal degradation, by in vitro and in vivo methods
| Autor: | Vadim A. Shevyrin, Geraldine Dowling, Pierce V. Kavanagh, Alexandr Pechnikov, Natalia Krupina, Andrew Labutin, Andrej Grigoryev |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Indoles Double bond Metabolite Pharmaceutical Science Urine 01 natural sciences Analytical Chemistry Hydroxylation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Biotransformation In vivo Tandem Mass Spectrometry Synthetic cannabinoids medicine Environmental Chemistry Animals Humans 030216 legal & forensic medicine Rats Wistar Spectroscopy Chromatography High Pressure Liquid chemistry.chemical_classification Chromatography Chemistry Cannabinoids 010401 analytical chemistry Temperature 0104 chemical sciences Substance Abuse Detection Carboxylation Microsomes Liver Metabolic Networks and Pathways medicine.drug Hair |
| Zdroj: | Drug testing and analysisREFERENCES. 11(9) |
| ISSN: | 1942-7611 |
| Popis: | Synthetic cannabinoids (SCs), mimicking the psychoactive effects of cannabis, consist of a vast array of structurally diverse compounds. A novel compound belonging to the SC family, (1-(cyclohexylmethyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (named TMCP-CHM in this article) contains a cyclopropane ring that isomerizes during the smoking process, resulting in a ring-opened thermal degradant with a terminal double bond in its structure. Metabolites of TMCP-CHM were tentatively identified in vitro (after incubation of the parent substance with S9 pooled human liver fraction) and in vivo (rat experimental model) studies by accurate-mass liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the identification of the degradant metabolites, and to study biotransformation of parent substance in the human, urine and hair samples from patients, who had ingested the compound and were subsequently admitted to hospital with drug intoxications, were analyzed. Products of mono-, di-, trihydroxylation, carboxylation, and carboxylation combined with hydroxylation of TMCP-CHM and its degradant were detected in human urine. Metabolism of the degradant included addition of water to the terminal double bond followed by dehydration and formation of a cyclic metabolite. Degradant metabolites prevailed in comparison with metabolites of the parent substance in each metabolite group examined, except carboxylation. N-Dealkylated metabolites found in human urine originated only from the degradant. Most of the hydroxy metabolites were detected in human urine in both the free form and as glucuronides. The detection of monohydroxylated (M1.1-M1.3, M/A1.10) and carboxylated/hydroxylated (M4.2, M/A4.3) metabolites of TMCP-CHM and the hydrated form of the monohydroxylated metabolite of the degradant was found to be convenient for routine analysis. |
| Databáze: | OpenAIRE |
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