Volume 11, Issue 9 p. 1387-1402
RESEARCH ARTICLE

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

Andrej Grigoryev

Corresponding Author

Andrej Grigoryev

Forensic-Chemical Division, Bureau of Forensic-Medical Expertise's, Moscow, Russia

Correspondence

Andrej Grigoryev, Bureau of Forensic-Medical Expertise's, Forensic-Chemical Division, 1th Vladimirskaya str. 33, build. 1, Moscow, Russia 111401.

Email: [email protected]

Search for more papers by this author
Pierce Kavanagh

Pierce Kavanagh

Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, Saint James's Hospital, Dublin, Ireland

Search for more papers by this author
Andrew Labutin

Andrew Labutin

Regional Drug Dependence Clinic, Tomsk, Russia

Search for more papers by this author
Alexandr Pechnikov

Alexandr Pechnikov

Internet-portal ‘Forum Forensic Experts in Russia’, Salekhard, Russia

Search for more papers by this author
Geraldine Dowling

Geraldine Dowling

Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre for Health Sciences, Saint James's Hospital, Dublin, Ireland

School of Science, Institute of Technology Sligo, Sligo, Ireland

Search for more papers by this author
Vadim Shevyrin

Vadim Shevyrin

Ural Federal University, Institute of Chemistry and Technology, Ekaterinburg, Russia

Search for more papers by this author
Natalia Krupina

Natalia Krupina

Forensic-Chemical Division, Bureau of Forensic-Medical Expertise's, Moscow, Russia

Search for more papers by this author
First published: 26 June 2019
Citations: 4

Abstract

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.