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

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.