TY - JOUR
T1 - Ultrafast, Selective, and Highly Sensitive Nonchromatographic Analysis of Fourteen Cannabinoids in Cannabis Extracts, Δ8-Tetrahydrocannabinol Synthetic Mixtures, and Edibles by Cyclic IonMobility Spectrometry−Mass Spectrometry
AU - Huang, Si
AU - Righetti, L.
AU - Claassen, Frank W.
AU - Krishna, Akash
AU - Ma, Ming
AU - van Beek, Teris A.
AU - Chen, Bo
AU - Zuilhof, Han
AU - Salentijn, Gert IJ.
PY - 2024
Y1 - 2024
N2 - 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 (TWCCSN2) 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, TWCCSN2, 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) (R2 = 0.9999), 0.1–25 ng·ml–1 for Δ9-THC (3) (R2 = 0.9987), and 0.04–10 ng·ml–1 for CBD (4) (R2 = 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 (R2 = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.
AB - 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 (TWCCSN2) 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, TWCCSN2, 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) (R2 = 0.9999), 0.1–25 ng·ml–1 for Δ9-THC (3) (R2 = 0.9987), and 0.04–10 ng·ml–1 for CBD (4) (R2 = 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 (R2 = 0.999) with those obtained by gas chromatography-flame ionization detection/mass spectrometry.
U2 - 10.1021/acs.analchem.3c05879
DO - 10.1021/acs.analchem.3c05879
M3 - Article
SN - 0003-2700
VL - 96
SP - 10170
EP - 10181
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 25
ER -