Rapid Distinction and Semiquantitative Analysis of THC and CBD by Silver-Impregnated Paper Spray Mass Spectrometry

Abstract

The control over the amount of psychoactive THC (Δ-9-tetrahydrocannabinol) in commercial cannabidiol (CBD) products has to be strict. A fast and simple semiquantitative Ag(I)-impregnated paper spray mass spectrometric method for differentiating between THC and CBD, which show no difference in standard single-stage or tandem MS, was established. Because of a different binding affinity to Ag(I) ions, quasi-molecular Ag(I) adducts [THC + Ag] + and [CBD + Ag] + at m / z 421 and 423 give different fragmentation patterns. The product ions at m / z 313 for THC and m / z 353 and 355 for CBD can be used to distinguish THC and CBD and to determine their ratio. Quantification of THC/CBD ratios in commercial CBD oils was accomplished with a low matrix effect (−2.2 ± 0.4% for THC and −2.0 ± 0.3% for CBD). After simple methanol extraction (recovery of 87.3 ± 1.2% for THC and 92.3 ± 1.4% for CBD), Ag(I)-impregnated paper spray analysis was employed to determine this ratio. A single run can be completed in a few minutes. This method was benchmarked against the UHPLC-UV method. Ag(I)-impregnated paper spray MS had the same working range (THC/CBD = 0.001–1) as UHPLC-UV analysis ( R 2 = 0.9896 and R 2 = 0.9998, respectively), as well as comparable accuracy (−2.7 to 14%) and precision (RSD 1.7–11%). The method was further validated by the analysis of 10 commercial oils by Ag(I)-impregnated paper spray MS and UHPLC-UV analysis. Based on the determined relative concentration ratios of THC/CBD and the declared CBD concentration, 6 out of 10 CBD oils appear to contain more THC than the Dutch legal limit of 0.05%.

A direct mass spectrometry method for cannabinoid quantitation in urine and oral fluid utilizing reactive paper spray ionization

“…24 Silver-impregnated paper has been used for THC and CBD analysis in edible oils, but at high concentrations (e.g., 200 ng mL −1 ), and it is unclear whether this technique could be applied to biofluid matrices. 16 Others used sesame oil to successfully preconcentrate analytes from larger sample volumes (50 µL) prior to analysis. 15 However, the technique involved manual cutting of paper strips after preconcentration/extraction and could not be successfully automated for THC-COOH measurements.…”

“…Some groups have increased sensitivity for cannabinoids with PS-MS, but at the cost of including undesirable reagents and/or additional sample preparation steps. 11,15,16 A less complex approach to increase sensitivity for cannabinoid measurements by PS-MS in biofluid samples could be the use of 'on-paper' derivatization (reactive paper spray mass spectrometry). In reactive PS-MS, small volumes (e.g., 10 µL) of reagents and samples are deposited on paper spray substrates to achieve favourable chemical reactions or study reaction conditions.…”

Ionization of glycans from alkali metal salt-impregnated paper

“…selectivity, sensitivity, and ionization efficiency [5][6][7][8][9][10][11][12]. Recently, a Ag + adduction strategy for the distinction of isomers, i.e., THC and CBD, by PS-MS was demonstrated by our group, which provided a compelling example of the idea that metal ion adduction is a powerful method to improve PS-MS performance [13].…”

Direct In Vivo Analysis of CBD- and THC-Acid Cannabinoids and Classification of Cannabis Cultivars Using SpiderMass

“…Thanks to the formation of molecular ions, the discrimination of THC and CBD has been made possible via MS/MS analysis [14]. Alternatively, paper spray MS has been used for the detection of THC and CBD in commercial oils through the use of a Ag(I)-impregnated paper [15]. Direct analysis or "swabbing" of cannabis leaves has also been evaluated using DESI-MS [16] and an atmospheric solids analysis probe (ASAP) using the positive ion mode [2].…”