Ultrafast, Selective, and Highly Sensitive Nonchromatographic Analysis of Fourteen Cannabinoids in Cannabis Extracts, Δ8-Tetrahydrocannabinol Synthetic Mixtures, and Edibles by Cyclic Ion Mobility Spectrometry-Mass Spectrometry.

The diversity of cannabinoid isomers and complexity of Cannabis products pose significant challenges for analytical methodologies. In this study, we developed a method to analyze 14 different cannabinoid isomers in diverse samples within milliseconds by leveraging the unique adduct-forming behavior of silver ions in advanced cyclic ion mobility spectrometry-mass spectrometry. The developed method achieved the separation of isomers from four groups of cannabinoids: Δ3-tetrahydrocannabinol (THC) (), Δ8-THC (), Δ9-THC (), cannabidiol (CBD) (), Δ8-iso-THC (), and Δ(4)8-iso-THC () (all MW = 314); 9α-hydroxyhexahydrocannabinol (), 9β-hydroxyhexahydrocannabinol (), and 8-hydroxy-iso-THC () (all MW = 332); tetrahydrocannabinolic acid (THCA) () and cannabidiolic acid (CBDA) () (both MW = 358); Δ8-tetrahydrocannabivarin (THCV) (), Δ8-iso-THCV (), and Δ9-THCV () (all MW = 286). Moreover, experimental and theoretical traveling wave collision cross section values in nitrogen (CCS) of cannabinoid-Ag(I) species were obtained for the first time with an average error between experimental and theoretical values of 2.6%. Furthermore, a workflow for the identification of cannabinoid isomers in Cannabis and Cannabis-derived samples was established based on three identification steps (/ and isotope pattern of Ag(I) adducts, CCS, and MS/MS fragments). Afterward, calibration curves of three major cannabinoids were established with a linear range of 1-250 ng·ml for Δ8-THC () ( = 0.9999), 0.1-25 ng·ml for Δ9-THC () ( = 0.9987), and 0.04-10 ng·ml for CBD () ( = 0.9986) as well as very low limits of detection (0.008-0.2 ng·ml). Finally, relative quantification of Δ8-THC (), Δ9-THC (), and CBD () in eight complex acid-treated CBD mixtures was achieved without chromatographic separation. The results showed good correspondence ( = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.