Cannabis and its cannabinoids analysis by gas chromatography–mass spectrometry with Cold EI

Cannabis extracts and products were analyzed by gas chromatography–mass spectrometry (GC–MS) with Cold EI for their full content including terpenes, sesquiterpenes, sesquiterpinols, fatty acids, delta 9‐tetrahydrocannabinol (THC), cannabidiol (CBD), other cannabinoids, hydrocarbons, sterols, diglycerides, triglycerides, and impurities. GC–MS with Cold EI 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 (hence the name Cold EI). GC–MS with Cold EI improves all the performance aspects of GC–MS, enables the analysis of Cannabinoids with OH groups without derivatization, while providing enhanced molecular ions for improved identification, and enables internal quantitation without calibration. We found over 50 cannabinoid compounds including a new one with a Cold EI mass spectrum very similar to delta 9‐THC as well as relatively large cannabinoids with molecular weight above m/z = 400. Because the analysis was universal in full scan and not targeted, we found impurities such as bromo CBD and fluticasone propionate and could monitor the formation of oxidized CBD during decarboxylation. In addition, GC–MS with Cold EI enabled nontargeted full analysis of terpenes, sesquiterpenes, and sesquiterpinols in cannabis extracts with good internal quantitation. GC–MS with Cold EI further served with very good sensitivity for the concentration determination of delta 9‐THC in CBD‐related products. Finally, cannabis drugs such as EP‐1 used in Israel for treatment of epilepsy and for children with autism spectrum disorder (ASD) were analyzed for their full cannabinoids content for learning on the entourage effect and for drug activity optimization.