Advanced search
2 files | 3.92 MB

Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system

(2017) ANALYTICAL CHEMISTRY. 89(17). p.9527-9536
Author
Organization
Abstract
Synthetic cannabinoids (SCs) continue to be the largest group of new psychoactive substances (NPS) monitored by the European Monitoring Center of Drugs and Drugs of Abuse (EMCDDA). The identification and subsequent prohibition of single SCs has driven clandestine chemists to produce analogues of increasing structural diversity, intended to evade legislation. That structural diversity, combined with the mostly unknown metabolic profiles of these new SCs, poses a big challenge for the conventional targeted analytical assays, as it is difficult to screen for "unknown" compounds. Therefore, an alternative screening method, not directly based on the structure but on the activity of the SC, may offer a solution for this problem. We generated stable CB1 and CB2 receptor activation assays based on functional complementation of a split NanoLuc luciferase and used these to test an expanded set of recent SCs (UR-144, XLR-11, and their thermal degradation products; AB-CHMINACA and ADB-CHMINACA) and their major phase I metabolites. By doing so, we demonstrate that several major metabolites of these SCs retain their activity at the cannabinoid receptors. These active metabolites may prolong the parent compound's psychotropic and physiological effects and may contribute to the toxicity profile. Utility of the generated stable cell systems as a first -line screening tool for SCs in urine was also demonstrated using a relatively large set of authentic urine samples. Our data indicate that the stable CB reporter assays detect CB receptor, activation by extracts of urine in which SCs (or their metabolites) are present at low- or subnanomolar (ng/mL) level. Hence, the developed assays do not only allow activity profiling of SCs and their metabolites, it may also serve as a screening tool, complementing targeted and untargeted analytical assays and preceding analytical (mass spectrometry based) confirmation.
Keywords
AB-CHMINACA, PYROLYSIS PRODUCT, MASS-SPECTROMETRY, MAB-CHMINACA, METABOLITES, IDENTIFICATION, AFFINITY, UR-144, QUANTIFICATION, INTOXICATION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 2.59 MB
  • postprint Activity-based detection.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 1.33 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Cannaert, Annelies, Florian Franz, Volker Auwärter, and Christophe Stove. 2017. “Activity-based Detection of Consumption of Synthetic Cannabinoids in Authentic Urine Samples Using a Stable Cannabinoid Reporter System.” Analytical Chemistry 89 (17): 9527–9536.
APA
Cannaert, A., Franz, F., Auwärter, V., & Stove, C. (2017). Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system. ANALYTICAL CHEMISTRY, 89(17), 9527–9536.
Vancouver
1.
Cannaert A, Franz F, Auwärter V, Stove C. Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system. ANALYTICAL CHEMISTRY. 2017;89(17):9527–36.
MLA
Cannaert, Annelies, Florian Franz, Volker Auwärter, et al. “Activity-based Detection of Consumption of Synthetic Cannabinoids in Authentic Urine Samples Using a Stable Cannabinoid Reporter System.” ANALYTICAL CHEMISTRY 89.17 (2017): 9527–9536. Print.
@article{8545685,
  abstract     = {Synthetic cannabinoids (SCs) continue to be the largest group of new psychoactive substances (NPS) monitored by the European Monitoring Center of Drugs and Drugs of Abuse (EMCDDA). The identification and subsequent prohibition of single SCs has driven clandestine chemists to produce analogues of increasing structural diversity, intended to evade legislation. That structural diversity, combined with the mostly unknown metabolic profiles of these new SCs, poses a big challenge for the conventional targeted analytical assays, as it is difficult to screen for "unknown" compounds. Therefore, an alternative screening method, not directly based on the structure but on the activity of the SC, may offer a solution for this problem. We generated stable CB1 and CB2 receptor activation assays based on functional complementation of a split NanoLuc luciferase and used these to test an expanded set of recent SCs (UR-144, XLR-11, and their thermal degradation products; AB-CHMINACA and ADB-CHMINACA) and their major phase I metabolites. By doing so, we demonstrate that several major metabolites of these SCs retain their activity at the cannabinoid receptors. These active metabolites may prolong the parent compound's psychotropic and physiological effects and may contribute to the toxicity profile. Utility of the generated stable cell systems as a first -line screening tool for SCs in urine was also demonstrated using a relatively large set of authentic urine samples. Our data indicate that the stable CB reporter assays detect CB receptor, activation by extracts of urine in which SCs (or their metabolites) are present at low- or subnanomolar (ng/mL) level. Hence, the developed assays do not only allow activity profiling of SCs and their metabolites, it may also serve as a screening tool, complementing targeted and untargeted analytical assays and preceding analytical (mass spectrometry based) confirmation.},
  author       = {Cannaert, Annelies and Franz, Florian and Auwärter, Volker and Stove, Christophe},
  issn         = {0003-2700},
  journal      = {ANALYTICAL CHEMISTRY},
  keywords     = {AB-CHMINACA,PYROLYSIS PRODUCT,MASS-SPECTROMETRY,MAB-CHMINACA,METABOLITES,IDENTIFICATION,AFFINITY,UR-144,QUANTIFICATION,INTOXICATION},
  language     = {eng},
  number       = {17},
  pages        = {9527--9536},
  title        = {Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system},
  url          = {http://dx.doi.org/10.1021/acs.analchem.7b02552},
  volume       = {89},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: