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
Si Huang, Laura Righetti, Frank W. Claassen, Akash Krishna, Ming Ma, Teris A. van Beek, Bo Chen, Han Zuilhof, Gert IJ. Salentijn
Abstract
High Resolution Image Download MS PowerPoint Slide 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) ( 1 ), Δ8-THC ( 2 ), Δ9-THC ( 3 ), cannabidiol (CBD) ( 4 ), Δ8-iso-THC ( 5 ), and Δ(4)8-iso-THC ( 6 ) (all MW = 314); 9α-hydroxyhexahydrocannabinol ( 7 ), 9β-hydroxyhexahydrocannabinol ( 8 ), and 8-hydroxy-iso-THC ( 9 ) (all MW = 332); tetrahydrocannabinolic acid (THCA) ( 10 ) and cannabidiolic acid (CBDA) ( 11 ) (both MW = 358); Δ8-tetrahydrocannabivarin (THCV) ( 12 ), Δ8-iso-THCV ( 13 ), and Δ9-THCV ( 14 ) (all MW = 286). Moreover, experimental and theoretical traveling wave collision cross section values in nitrogen ( TW CCS N2 ) 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 ( m / z and isotope pattern of Ag(I) adducts, TW CCS N2, and MS/MS fragments). Afterward, calibration curves of three major cannabinoids were established with a linear range of 1–250 ng·ml –1 for Δ8-THC ( 2 ) ( R 2 = 0.9999), 0.1–25 ng·ml –1 for Δ9-THC ( 3 ) ( R 2 = 0.9987), and 0.04–10 ng·ml –1 for CBD ( 4 ) ( R 2 = 0.9986) as well as very low limits of detection (0.008–0.2 ng·ml –1 ). Finally, relative quantification of Δ8-THC ( 2 ), Δ9-THC ( 3 ), and CBD ( 4 ) in eight complex acid-treated CBD mixtures was achieved without chromatographic separation. The results showed good correspondence ( R 2 = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.