Characterization of copper-phosphine complexes for the differentiation of cannabinoid isomers using electrospray ionization-tandem mass spectrometry

The 2018 Agriculture Improvement Act provides the distinction between illicit marijuana and legal hemp based on a 0.3% ∆ 9 -tetrahydrocannabinol (∆ 9 -THC) threshold. Consequently, forensic laboratories and regulatory agencies must implement analytical methods capable of qualitative identification and quantification of ∆ 9 -THC. Analysis is further complicated by the complex matrix of Cannabis sativa L., which contains various cannabinoid isomers. While liquid chromatography-mass spectrometry (LC-MS) precludes cannabinoid decarboxylation and cannabinoid conversion limitations inherent to gas chromatography–mass spectrometry (GC–MS), ∆ 9 -THC isomers remain nearly indistinguishable in both full scan and product ion mass spectra. This study characterizes 11 Cu-phosphine complexes to assess their ability to differentiate common cannabinoids found in cannabis plant material, as well as ∆ 9 -THC isomers that may be sprayed onto plant material, based on the formation of characteristic precursor or product ions. Specifically, the preferential binding affinity of cannabinoids to [Cu(PPh 3 ) 2 (ACN) 2 ]BF 4 , in combination with oxidative products generated through Cu-catalyzed O 2 activation, facilitates the formation of a characteristic ion at nominal m/z 915 for ∆ 9 -THC and no observable complex for CBD, enabling full scan isomer differentiation and eliminating potential CBD interference for ∆ 9 -THC quantitation. Similar behavior was observed for [Cu( (R)- BINAP)(ACN) 2 ]BF 4 and [Cu(dppf)(ACN) 2 ]BF 4 . A methanolic extract of an authentic cannabis sample was analyzed using the optimal Cu-phosphine complexes to evaluate applicability to real-world samples. By demonstrating the potential of Cu-phosphine ion complexation and introducing a novel approach to eliminate CBD interference, this study establishes the foundation for future research distinguishing illicit marijuana from legal hemp, potentially strengthening the capabilities of marijuana identification within forensic laboratories.