Abstract
Synthetic cannabinoids (SCs) are consumed as legal alternative to cannabis and often allow passing drug-screening tests. Their rapid transience on the drug scene, combined with their mostly unknown metabolic profiles, creates a scenario with constantly moving analytical targets, making their monitoring and identification challenging. The development of fast screening strategies for SCs, not directly focused on their chemical structure, as an alternative to the commonly applied target acquisition methods, would be highly appreciated in forensic and public health laboratories. An innovative untargeted metabolomics approach, focused on herbal components commonly used for ‘spice’ products, was applied. Saliva samples of healthy volunteers were collected at pre-dose and after smoking herbal components and analysed by high-resolution mass spectrometry. The data obtained, combined with appropriate statistical analysis, allowed to highlight and elucidate two markers (scopoletin and N,N-bis(2-hydroxyethyl)dodecylamine), which ratio permitted to differentiate herbal smokers from non-smokers. The proposed strategy will allow discriminating potential positives, on the basis of the analysis of two markers identified in the herbal blends. This work is presented as a step forward in SC drug testing, promoting a smart first-line screening approach, which will allow reducing the number of samples to be further investigated by more sophisticated HRMS methods.
References
EMCDDA. Understanding the ‘Spice’ phenomenon [Internet]. 2009. Available from: http://www.emcdda.europa.eu/publications/thematic-papers/spice
UNODC. Market analysis of synthetic drugs: Amphetamine-type stimulants, new psychoactive substances. In: World Drug Report 2017 [Internet]. 2017. p. 60. Available from: http://www.unodc.org/documents/scientific/Booklet_4_Market_Analysis_of_Synthetic_Drugs_ATS_NPS.pdf
Seely KA, Lapoint J, Moran JH, Fattore L. Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuro-Psychopharmacology Biol Psychiatry [Internet]. 2012;39(2):234–43. Available from: https://doi.org/10.1016/j.pnpbp.2012.04.017
van Amsterdam J, Brunt T, van den Brink W. The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects. J Psychopharmacol [Internet] 2015;29(3):254–263. Available from: http://journals.sagepub.com/doi/10.1177/0269881114565142
Angerer V, Jacobi S, Franz F, Auwärter V, Pietsch J. Three fatalities associated with the synthetic cannabinoids 5F-ADB, 5F-PB-22, and AB-CHMINACA. Forensic Sci Int [Internet]. 2017;281:e9–15. Available from: https://doi.org/10.1016/j.forsciint.2017.10.042
Bijlsma L, Ibáñez M, Miserez B, Ma STF, Shine T, Ramsey J, et al. Mass spectrometric identification and structural analysis of the third-generation synthetic cannabinoids on the UK market since the 2013 legislative ban. Forensic Toxicol. 2017;35(2):376–88.
Uchiyama N, Kikura-Hanajiri R, Ogata J, Goda Y. Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. Forensic Sci Int [Internet]. 2010;198(1–3):31–8. Available from: https://doi.org/10.1016/j.forsciint.2010.01.004
Shanks KG, Dahn T, Behonick G, Terrell A. Analysis of first and second generation legal highs for synthetic cannabinoids and synthetic stimulants by ultra-performance liquid chromatography and time of flight mass spectrometry. J Anal Toxicol. 2012;36(6):360–71.
Grabenauer M, Krol WL, Wiley JL, Thomas BF. Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs. Anal Chem. 2012;84(13):5574–81.
Ibáñez M, Bijlsma L, Van Nuijs ALN, Sancho JV, Haro G, Covaci A, et al. Quadrupole-time-of-flight mass spectrometry screening for synthetic cannabinoids in herbal blends. J Mass Spectrom. 2013;48(6):685–94.
Cannaert A, Franz F, Auwärter V, Stove CP. Activity-based detection of consumption of synthetic cannabinoids in authentic urine samples using a stable cannabinoid reporter system. Anal Chem. 2017;89(17):9527–36.
EMCDDA. Perspectives on drugs: synthetic cannabinoids in Europe [Internet]. 2015. Available from: http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids
Malkar A, Devenport NA, Martin HJ, Patel P, Turner MA, Watson P, et al. Metabolic profiling of human saliva before and after induced physiological stress by ultra-high performance liquid chromatography–ion mobility–mass spectrometry. Metabolomics. 2013 Dec;9(6):1192–201.
Ogata J, Uchiyama N, Kikura-Hanajiri R, Goda Y. DNA sequence analyses of blended herbal products including synthetic cannabinoids as designer drugs. Forensic Sci Int [Internet]. 2013;227(1–3):33–41. Available from: https://doi.org/10.1016/j.forsciint.2012.09.006
WHO. The health and social effects of nonmedical cannabis use [Internet]. World Health Organization. Geneva, Switzerland; 2016. Available from: http://who.int/substance_abuse/publications/msbcannabis.pdf?ua=1.
Raro M, Ibáñez M, Gil R, Fabregat A, Tudela E, Deventer K, et al. Untargeted metabolomics in doping control: detection of new markers of testosterone misuse by ultrahigh performance liquid chromatography coupled to high-resolution mass spectrometry. Anal Chem. 2015;87(16):8373–80.
Chekmeneva E, Dos Santos Correia G, Chan Q, Wijeyesekera A, Tin A, Young JH, et al. Optimization and application of direct infusion nanoelectrospray HRMS method for large-scale urinary metabolic phenotyping in molecular epidemiology. J Proteome Res. 2017;16(4):1646–58.
Patti GJ, Yanes O, Siuzdak G. Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol [Internet]. 2012 Mar 22;13:263–9. Available from: https://doi.org/10.1038/nrm3314
Li X, Martinez-Lozano Sinues P, Dallmann R, Bregy L, Hollmén M, Proulx S, et al. Drug pharmacokinetics determined by real-time analysis of mouse breath. Angew Chemie - Int Ed. 2015;54(27):7815–8.
Want EJ, Wilson ID, Gika H, Theodoridis G, Plumb RS, Shockcor J, et al. Global metabolic profiling procedures for urine using UPLC-MS. Nat Protoc [Internet]. 2010;5(6):1005–18. Available from: https://doi.org/10.1038/nprot.2010.50
Acknowledgments
The authors would like to thank CSM, RGS and RBvL for their collaboration in providing saliva samples.
Funding
Lubertus Bijlsma acknowledges NPS-Euronet (HOME/2014/JDRUG/AG/DRUG/7086), co-funded by the European Union, for his post-doctoral fellowship. This publication reflects the views only of the authors, and the European Commission cannot be held responsible for any use which may be made of the information contained therein. The authors acknowledge the financial support of Generalitat Valenciana (Prometeo II 2014/023) and the Spanish Ministry of Economy and Competitiveness (Project ref. CTQ2015-65603).
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The study was approved by the ethics committee (la Comisión Deontológica) of the University Jaume I and was conducted in accordance with the ethical standards, considering the Declaration of Helsinki. The healthy volunteers signed an informed consent.
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The authors declare that they have no conflicts of interest.
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Bijlsma, L., Gil-Solsona, R., Hernández, F. et al. What about the herb? A new metabolomics approach for synthetic cannabinoid drug testing. Anal Bioanal Chem 410, 5107–5112 (2018). https://doi.org/10.1007/s00216-018-1182-8
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DOI: https://doi.org/10.1007/s00216-018-1182-8