Literature Seminar

The 2012 Food and Drug Administration Safety and Innovation Act placed 26 types of cannabinoid receptor agonists, also known as synthetic cannabinoids (SCs) into Schedule 1 of the Controlled Substances Act. This decision was made due to SCs high probability of causing adverse health effects, like reduced blood supply to the heart, kidney damage, seizures, and even death.^1-3 Despite this, the SC industry has frequently altered the chemical structure of their products to avoid the ban and have continued selling under different names and brands.¹ Testing for SC metabolites in humans differs from conventional cannabinoid tests (immunoassays), due to the structural diversity of SCs.⁴ A rising method for identification of these new compounds and their metabolites is liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (LC-QTOF). The study discussed used LC-QTOF to identify the metabolites of (1-(cyclohexylmethyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (TMCP-CHM) and the product of its thermal degradation. Both in vitro and in vivo studies were performed, and the products analyzed using LC-QTOF. The major metabolic pathways were identified, and the results of the in vivo and in vitro studies were compared to a study performed on a compound with the TMCP moiety in human urine. This led to the identification of a convenient target for routine analysis and a trend in the metabolism of three compounds containing the TMCP moiety.⁵ With this study as a prevalent example, it was determined that LC-QTOF is a more ideal method for separation and primary identification of SCs and their metabolites in human urine in comparison to immunoassays and other industry standards, such as gas chromatography mass spectrometry (GC-MS) or liquid chromatography triple quadrupole mass spectrometry (LC-QQQ).

1. Hudson, S; Ramsey, J. The emergence and Analysis of Synthetic Cananbinoids. Drug Testing and Analysis 2011, 3 (7-8), 466-478.
2. Food and Drug Administration Safety and Innovation Act; 112 Congress, 2012; Public Law No. 112-114
3. National Institute on Drug Abuse. Synthetic Cannabinoids (K2/Spice) Drug Facts. https://www.drugabuse.gov/publications/drugfacts/synthetic-cannabinoids-k2spice
4. Franz, F.; et. al. Immunoassay Screening In Urine for Synthetic Cannabinoids – An Evaluation of the Diagnostic Efficiency. Clinical Chemistry and Laboratory Medicine (CCLM) 2017, 55 (9).
5. Grigoryev, A.; Kavanagh, P; Labutin, A.; Pechnikov, A.; Dowling, G.; Shevyrin, V.; Krupina, N. 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. Drug Testing and Analysis 2019, 11 (9), 1387-1402