Cannabis and cannabinoid analysis by GC-MS with Cold EI

Written by Sabina Pulone

The application of gas chromatography (GC) coupled with mass spectrometry (MS) is a widely used analytical method for cannabis plants and extracts. Molecules containing polar groups like hydroxyls (-OH), carboxyls (-COOH), etc. have to be derivatized prior to the analysis because of their decomposition at the standard electron ionization (EI) ion sources: the capping of labile groups like the acidic moiety of tetrahydrocannabinolic acid (THCA) through protective groups like trimethylsilyl ethers can ensure a proper analysis outcome, but the derivatization step is time consuming and involves drying procedures that could be particularly laborious in the case of cannabis oils, resins, and concentrates. [1]

Depending on the kind of equipment used, sample preparation, injection, and ionization methods, the sensitivity of the MS paired with GC can be improved, resulting in reliable phytochemical quantification and characterization of cannabis varieties and extracts. GC-MS with cold EI is a valuable analytical technique capable of providing uniform compound response in a non-targeted analysis of cannabis extracts, products, and drug derivatives. [2]

This method is based on interfacing GC and MS with supersonic molecular beams (SMB) along with electron ionization of vibrationally cold sample compounds in the SMB in a fly-through ion source. A SMB is formed by sending gas (e.g., helium carrier gas) through a small orifice from a region of higher pressure to one of lower pressure (i.e., a vacuum chamber), thereby cooling the sample and expanding and accelerating the gas faster than the speed of sound (along with the sample). The cold sample is ionized without touching the walls of the ion source, thus maintaining an approximately uniform electron ionization yield. GC-MS with cold EI provides various advantages like enhanced molecular ions, improved sample identification, extended range of compounds that can be analysed, internal quantitation, lower detection limits, greater selectivity, and faster analysis. [2]

With this analytical method, it is possible to calculate the abundance of each analyte without prior calibration curve measurements, including cannabinoids. Moreover, cold EI permits the analysis of compounds containing -OH moieties without prior derivatization; with standard EI, -OH groups tend to react with the metallic ion source and decompose, leading to a nonlinear response, while in cold EI with contact-free fly-through ionization, this problem is avoided, making this method suitable for cannabinoids and other compounds containing labile groups. The comprehensive untargeted analysis through GC-MS with cold EI provides information on the full content of cannabis sample compounds; through this kind of analysis, it is possible to detect and quantify a wide range of compounds including volatile terpenes, sesquiterpenes, fatty acids, cannabinoids, hydrocarbons, sterols, glycerides, and impurities. As an example of the latter, researchers exploring this method detected a nasal spray drug in cannabis flower that would not have been detected using GC-MS. [2] They also discovered a new cannabinoid with similar structure to delta-9-tetrahydrocannabinol (THC) which they named THC-Aviv.

GC-MS with cold EI has the advantage of providing a comprehensive analysis of a complex cannabis mixture, reporting the presence of unexpected substances in the sample in addition to traces of pesticides. This method can be particularly suitable for forensic cases and monitoring cannabis edibles. It can also serve for learning about the entourage effect for the optimization of cannabis-based drug efficiency. [2]




[1] Fodor B, et al. The role of derivatization techniques in the analysis of plant cannabinoids by gas chromatography mass spectrometry. Trends in Analytical Chemistry. 2017. S0165993617301826. doi:10.1016/j.trac.2017.07.022. [Journal Impact Factor = 12.296] [Times cited = 14 (Semantic Scholar)]


[2] Amirav A, et al. Cannabis and its cannabinoids analysis by gas chromatography–mass spectrometry with Cold EI. Journal of Mass Spectrometry. 2021;56(6). [Journal Impact Factor = 1.982] [Times cited = n/a]


Image: Cannabis to be analysed_Picture Sabina Pulone

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Sabina Pulone

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