Argentination: A Silver Bullet for Cannabinoid Separation by Differential Mobility Spectrometry

As the legality of cannabis continuesto evolve globally, thereis a growing demand for methods that can accurately quantitate cannabinoidsfound in commercial products. However, the isobaric nature of manycannabinoids, along with variations in extraction methods and productformulations, makes cannabinoid quantitation by mass spectrometry(MS) challenging. Here, we demonstrate that differential mobilityspectrometry (DMS) and tandem-MS can distinguish a set of seven cannabinoids,five of which are isobaric: Delta(9)-tetrahydrocannabinol(Delta(9)-THC), Delta(8)-THC, exo-THC, cannabidiol,cannabichromene, cannabinol, and cannabigerol. Analytes were detectedas argentinated species ([M + Ag](+)), which, when subjectedto collision-induced dissociation, led to the unexpected discoverythat argentination promotes distinct fragmentation patterns for eachcannabinoid. The unique fragment ions formed were rationalized bydiscerning fragmentation mechanisms that follow each cannabinoid'sMS(3) behavior. The differing fragmentation behaviors betweenspecies suggest that argentination can distinguish cannabinoids bytandem-MS, although not quantitatively as some cannabinoids producesmall amounts of a fragment ion that is isobaric with the major fragmentgenerated by another cannabinoid. By adding DMS to the tandem-MS workflow,it becomes possible to resolve each cannabinoid in a pure N-2 environment by deconvoluting the contribution of each cannabinoidto a specific fragmentation channel. To this end, we used DMS in conjunctionwith a multiple reaction monitoring workflow to assess cannabinoidlevels in two cannabis extracts. Our methodology exhibited excellentaccuracy, limits of detection (10-20 ppb depending on the cannabinoid),and linearity during quantitation by standard addition (R (2) > 0.99).