Differentiation of Δ 9 -THC and CBD Using Silver-Ligand Ion Complexation and Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS)

• Published in: Journal of the American Society for Mass Spectrometry 2024-07, Vol.35 (7), p.1413-1421
• Main Authors: Couch, Alleigh N, Lanza, Jayleigh M, Zall, Christopher M, Davidson, J Tyler
• Format: Article
• Language: English
• Subjects: Cannabidiol - analysis; Cannabidiol - chemistry; Cannabis - chemistry; Dronabinol - analysis; Dronabinol - chemistry; Ions - chemistry; Ligands; Silver - chemistry; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods
• ISSN: 1044-0305; 1879-1123
• DOI: 10.1021/jasms.3c00452

The 2018 Farm Bill defines marijuana as L. or any derivative thereof that contains greater than 0.3% Δ -tetrahydrocannabinol (Δ -THC) on a dry weight basis. The main cannabinoids present in L., Δ -THC and cannabidiol (CBD), are structural isomers that cannot be differentiated using direct mass spectrometry with soft ionization techniques alone. Due to the classification of marijuana as a Schedule I controlled substance, the differentiation of Δ -THC and CBD is crucial within the seized drug community. This study explores the use of Ag-ligand ion complexation and electrospray ionization tandem mass spectrometry (ESI-MS/MS) for the differentiation of Δ -THC and CBD using six different Ag complexes. Differences between the binding affinities of Δ -THC and CBD for [Ag(PPh )(OTf)] lead to the formation of unique product ions at / 421/423, / 353/355, and / 231 for CBD, enabling the differentiation of CBD from Δ -THC. When applied to the analysis of known Δ -THC:CBD mixture ratios, the developed [Ag(PPh )(OTf)] ion complexation method was able to differentiate Δ -THC-rich and CBD-rich samples based on the average abundance of the product ions at / 421/423. The developed approach was then applied to methanolic extracts of 20 authentic cannabis samples with known Δ -THC and CBD compositions, resulting in a 95% correct classification rate. Even though the developed Ag-ligand ion complexation method was only demonstrated for the qualitative differentiation of Δ -THC-rich and CBD-rich cannabis, this study establishes a foundation for the use of Ag-ligand ion complexation that is essential for future quantitative approaches.