Synthetic cannabinoids are among an expanding group of designer drugs that mimic the effects of controlled substances while evading regulation. Compared to cannabis, synthetic cannabinoids are often more potent, with active metabolites that remain in the brain longer. Of further concern, synthetic cannabinoids can cause very serious reactions, such as convulsions, elevated heart rate, increased blood pressure, vomiting, hallucinations, and even death.
Many countries have banned specific synthetic cannabinoid forms. However, as soon as a form is banned, a new isomer, derivative, or other novel variant is developed to replace it. A challenge to traditional forensics (link to forensics community) methods, only a small change in structure will render a molecule outside current regulation and undetectable.
Challenge to Traditional GC-MS and LC-MS Screening Methods
Synthetic cannabinoids are commonly analyzed using gas chromatography-mass spectrometry (GC-MS) (link to product page) and liquid chromatography-mass spectrometry (LC-MS) quantitation methods (link to application note abstract) that require reference material for confident identification and quantification. With the constant introduction of novel molecules for which there are no standards, methods that can detect and quantify both known and unknown synthetic cannabinoids at trace levels in matrices such as urine are urgently needed.
High-Resolution Accurate-Mass (HRAM) Solution
To address this problem, Dave Strong and Simon Hudson of LGC (formerly HFL Sport Science), Cambridgeshire, UK, developed a high-resolution accurate-mass (HRAM) LC-MS (link to product page) method that relies on the Thermo ScientificTM AccelaTM LC system coupled to the hybrid ion trap-Orbitrap mass spectrometer (link to product page).
In their article in the Analytical Scientist, Tracking Designer Drugs (link to article), Strong and Hudson describe how HRAM MS capability significantly improved the speed, selectivity and capacity of synthetic cannabinoid detection. Most importantly, however, the method made it possible to identify unknown synthetic cannabinoid metabolites.
Nominal Mass vs. Accurate Mass
Though many synthetic cannabinoid structures have the same nominal mass, their accurate masses are different and can be resolved using full-scan HRAM LC-MS. Subsequent MS/MS data can be used to determine isomeric structures. Both capabilities reduce the need for reference materials for screening and identification.
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To demonstrate the capabilities of the HRAM LC-MS method, the authors analyzed five synthetic cannabinoids: JWH-018, JWH-073, JWH-200, JWH-250 and AM-69, spiked in urine at 50 ng/mL. Because direct injection of urine can cause ion suppression and matrix interferences, the authors performed solid phase extraction (SPE) to purify and concentrate samples prior to LC-MS analysis.
To screen for known cannabinoids, full-scan HRAM LC-MS data were analyzed using automated screening software (link to product page). The ToxID software database includes information for cannabinoids and their metabolites. The database can be updated, enabling labs to retroactively screen HRAM data from previously analyzed samples for new compounds. When standards are available or when compounds have been detected previously, retention times can aid in screening.
The authors tested their method on urine samples obtained from a patient suspected of smoking a synthetic cannabinoid containing herbal product, and they concluded that the identification of the unknown synthetic cannabinoid metabolites would be nearly impossible without HRAM MS capability.
For more information about synthetic cannabinoids, visit the useful resources below.
- On-demand webinar: Close your uncertainty gap with High Resolution Mass Spectrometry
- DrugFacts: K2/Spice (Synthetic Marijuana) National Institute on Drug Abuse. December 2012.
- Synthetic cannabinoids and ‘Spice’ drug profile, European Monitoring Centre for Drugs and Drug Addiction.
- Chemicals Used in “Spice” and “K2” Type Products Now Under Federal Control and Regulation. News Release. Public Affairs, S. Drug Enforcement Administration. March 1, 2010.
- Notice of Intent to Temporarily Control Five Synthetic Cannabinoids. Office of Diversion Control, U.S. Department of Justice, Drug Enforcement Administration, Federal Register Notices, Rules – 2011.
Does your lab analyze synthetic cannabinoids? If so, I’d like to hear about your process and experience.