A growing number of papers suggest the positive action of cannabinoids in the treatment of several diseases, which is ascribed to the ability of phytocannabinoids to affect the human endocannabinoid system. In particular, this activity is characteristic of CBD, a non-psychoactive variation of 9-THC. It initiated a trend in the manufacturing of edible and cosmetic products containing CBD that can be easily acquired in drugstores. However, the composition of such products has rarely been tested. Hence, there is a need for data regarding their safety. Considering the possibility of cannabinoid interconversions as well as the complexity and diversity of edible products’ matrix, their analysis requires a suitable preparation and cleanup procedure. In this paper, the perspective of the application of Supercritical Fluid Chromatography (SFC) coupled to High-Resolution (HR) Quadrupole-Time of Flight (Q-TOF) tandem mass spectrometry (MS/MS) with electrospray ionization (ESI) in quality control of cannabis-containing food products was examined. The focus is on six neutral (CBD, 9-THC, CBC, CBG, CBN, and THCV) and three acidic (CBDA, THCA, and CBGA) cannabinoids. The study covers the thorough optimization of conditions for chromatographic separation with the use of the supercritical CO2 (scCO2)-based mobile phase and the working parameters of MS/MS detection with the elucidation of fragmentation patterns. Thanks to the utilization of scCO2, a short analysis time of 17 min., high intensity and small width of peaks, as well as low consumption of toxic organic solvent have been achieved at the 2-EP column with a 5 μm grain size. To reach such performance in LC, the utilization of more expensive columns packed with sub-2 μm particles is needed. In the case of the solvent matrix, the LOD was equal to 8 ng mL−1 for CBDA, THCA, and CBGA, 15 ng mL−1 for CBG and THCV, and 21 ng mL−1 for THC, CBD, CBC, and CBN. In the case of tea, an LOD of 25 ng mL−1 for acidic and 75 ng mL−1 for neutral cannabinoids has been obtained. The accuracy and precision were within the ± 15 % tolerance limit. Finally, the devised protocol has been applied for cannabinoid determination in hemp tea infusions.
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