Synthetic Cannabinoids Degradation Studied Using GC–MS


Scientists from the Naif Arab University for Security Sciences in Riyadh, Saudi Arabia used a new approach to protect amide-based synthetic cannabinoids from degradation and esterification during gas chromatography–mass spectrometry (GC–MS) analysis. Their findings were published in the Journal of Chromatography A (1).

synthetic marijuana: laboratory technician holds samples of narcotic herbal medicines in hand | Image Credit: © BUSLIQ -

synthetic marijuana: laboratory technician holds samples of narcotic herbal medicines in hand | Image Credit: © BUSLIQ -

Synthetic cannabinoids (SCs) are laboratory-made substances that are like chemicals found in the cannabis plant (2). SCs are a group of new psychoactive substances that mimic the effects of natural cannabinoids. SCs are commonly sold as herbal compounds and powders. Though recently, SCs have been sold as tablets, capsules, or in combination with other illicit drug tablets, such as amphetamines, tramadol, and cathinone. The growing use of SCs among consumers has made it more important for scientists to find better methods of analysis and sample preparation.

Extracting SCs from materials, like herbs, powders, and tablets, is commonly performed via solvent extraction using methanol (MeOH), ethanol (EtOH), or ethyl acetate (EtOAc). Gas chromatography–mass spectrometry (GC–MS) is often used in routine forensic analysis for identifying and quantifying SCs in seized materials, mostly due to it providing identification capabilities within National Institute of Standards and Technology (NIST) and Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG) mass spectra libraries. However, there are some issues with GC–MS use, including the thermolytic degradation of substances with functional groups.

For this study, the scientists reported the comprehensive thermal degradation and ester transformation of amide-based SCs, such as methyl (S)−2-[1-(4-fluorobenzyl)−1H-indazole-3-carboxamido]−3-methylbutanoate (AB-FUBINACA), methyl ester (AB-CHMINACA), and N-[1-(aminocarbonyl)−2,2-dimethylpropyl]−1(cyclohexylmethyl)−1H-indazole-3-carboxamide (MAB-CHMINACA), during GC–MS analysis and treatment with analyte protectants (APs). These SCs were found to undergo thermolytic degradation during GC–MS in the presence of non-alcohol solvents. When methanol was used as an injection solvent, amide groups were converted to ester groups, producing other SCs. Degradant and ester product formation was interpreted as the adsorption of target SCs on glass wool via hydrogen bonding interactions between the active silanol and amide groups of the SCs, followed by an addition or elimination process. The factors found to influence the thermal degradation or esterification of the amide functional group include residence time, activity of glass wool, and injection volume.

Further, this report shows the fragmentation patterns of all compounds produced by degradation and esterification. Using 0.5% sorbitol (AP) in MeOH as an injection solvent resulted in complete protection and improvement of the chromatographic shape of the compounds. In fact, using 0.5% sorbitol in MeOH, the method was successfully confirmed in terms of sensitivity, linearity, accuracy, and precision for standard solutions and tablet extraction. Using APs increased sensitivity by 10 times or more compared with when only MeOH was used. The limit of detection (LOD) for all analytes was determined as 25 ng/mL, and the calibration curves were linear over the concentration range of 50–2000 ng/mL. The values of accuracy error were below 11%, and precision was less than 13%. Altogether, GC–MS analysis of MeOH with SCs containing amide group, when done with a liner with glass wool in splitless mode can result in a decrease in LOD and limit of quantification (LOQ) values, while potentially leading to substance mischaracterization owing to their conversion into other SCs.


(1) Masoud, K. M. M.; Syed, S. M.; Alasiri, A. M. Analyte Protectant Approach to Protect Amide-Based Synthetic Cannabinoids from Degradation and Esterification During GC–MS Analysis. J. Chromatogr. A 2024, 1730, 465022. DOI: 10.1016/j.chroma.2024.465022

(2) Synthetic Cannabinoids. National Institute on Drug Abuse 2024. (accessed 2024-6-26)

(3) Synthetic Cannabinoids. America’s Poison Centers 2024. (accessed 2024-6-26)

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