Cannabigerol (CBG) signal enhancement in its analysis by gas chromatography coupled with tandem mass spectrometry

• Published in: Forensic toxicology Vol. 42; no. 1; pp. 31 - 44
• Main Authors: Dawidowicz, Andrzej L., Typek, Rafal, Dybowski, Michal P., Holowinski, Piotr, Rombel, Michal
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.01.2024
• Subjects: Cannabidiol - analysis; Cannabinoids; Cannabinol - analysis; Forensic Medicine; Forensic Science; Gas Chromatography-Mass Spectrometry; Medical Law; Medicinal Chemistry; Medicine; Medicine & Public Health; Original; Original Article; Pharmacology/Toxicology; Tandem Mass Spectrometry - methods; Signal enhancement; GC–MS; CBG cyclization; Sample derivatization; Cannabigerol
• ISSN: 1860-8965; 1860-8973
• DOI: 10.1007/s11419-023-00673-x

Purpose According to recent reports, cannabigerol (CBG) concentration level in blood and body fluids may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking. While the analytical sensitivity of cannabidiol (CBD), Δ 9 -tetrahydrocannabinol (Δ 9 -THC), cannabichromene (CBC) or cannabinol (CBN) estimation by gas chromatography-mass spectrometry (GC–MS) is similar and sufficiently high, it is exceptionally low in the case of CBG (ca. 25 times lower than for the other mentioned cannabinoids). The purpose of this study is to explain the reasons for the extremely low analytical sensitivity of GC–MS in estimating CBG and to present possible ways of its improvement. Methods Nuclear magnetic resonance (NMR) data and GC–MS responses to CBG and its various derivatization and transformation products were studied. Results The validation data of individual derivatives of CBG and its transformation products were established. CBG silylation/acylation or hydration allows to decrease LOD about 3 times, whereas the formation of pyranic CBG derivative leads to 10-times decrease of LOD. The paper enriches the literature of the subject by providing MS and NMR spectra, not published so far, for derivatives of CBG and its transformation products. The most likely cause of low GC–MS response to CBG is also presented. Conclusions The presented results shows that although the signal increase of CBG can be obtained through its derivatization by silylation and/or acylation, the greatest increase is observed in the case of its cyclization to the pyranic CBG form during the sample preparation process. The CBG cyclization procedure is very simple and workable in estimating this cannabinoid in blood/plasma samples. Graphical abstract