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

The 2018 Farm Bill defines marijuana as Cannabis sativa L. or any derivative thereof that contains greater than 0.3% Δ ⁹ -tetrahydrocannabinol (Δ ⁹ -THC) on a dry weight basis. The main cannabinoids present in Cannabis sativa L., Δ ⁹ -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 ⁹ -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 ⁹ -THC and CBD using six different Ag complexes. Differences between the binding affinities of Δ ⁹ -THC and CBD for [Ag(PPh ₃ )(OTf)] ₂ lead to the formation of unique product ions at m / z 421/423, m / z 353/355, and m / z 231 for CBD, enabling the differentiation of CBD from Δ ⁹ -THC. When applied to the analysis of known Δ ⁹ -THC:CBD mixture ratios, the developed [Ag(PPh ₃ )(OTf)] ₂ ion complexation method was able to differentiate Δ ⁹ -THC-rich and CBD-rich samples based on the average abundance of the product ions at m / z 421/423. The developed approach was then applied to methanolic extracts of 20 authentic cannabis samples with known Δ ⁹ -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 ⁹ -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.