Computational and Design of Experiment Strategies to Improve Differentiation and Quantitation of Trace-Level Cannabinoids by Copper Cationization Paper Spray Mass Spectrometry

Despite this, current analytical methods have compromises when analyzing common isobaric cannabinoids, such as cannabidiol (CBD) or (−)-trans-Δ9-tetrahydrocannabinol (THC). We report on the use of computational chemistry, combined with design of experiment (DoE), to optimize and develop a paper spray mass spectrometry method with on-paper cationization to simplify workflow for trace level differentiation and quantitation of THC and CBD.

Computational chemistry allowed for pre-screening of candidate metal ions prior to experimental measurements, with promising candidates then being evaluated by electrospray ionization high resolution mass spectrometry (ESI-HRMS). A direct mass spectrometry method using copper cationization with paper spray mass spectrometry (PS-MS) was then developed and optimized using DoE. Copper cationization with both ESI and PS-MS tandem mass spectrometry demonstrated the best CBD/THC selectivity and sensitivity, with ~1% interference between [CuCBD]+ and [CuTHC]+, allowing rapid direct mass spectrometry differentiation.