Cannabidiol (CBD), a major non-psychoactive cannabinoid, has received a lot of attention due to its potential anti-inflammatory, pain-relieving, and anti-anxiety properties. This has led to a recent boom in CBD-rich commercial products, which are sold without prescription in the form of oils, candies, and cosmetics. Since these products are derived from cannabis, the presence of the psychoactive tetrahydrocannabinol (THC) has to be tested before they enter the market. Here, we present a high-throughput approach based on liquid chromatography coupled to UV and tandem mass spectrometric detection for the determination of CBD, THC, and six other minor cannabinoids (cannabigerolic acid, cannabidivarin, cannabinol, cannabigerol, cannabidiolic acid, and tetrahydrocannabinolic acid) in a wide range of concentrations and in a variety of matrices, including oils, hydrophobic ointments, water-soluble liquids, plant material and gelatinous gummies. Each product was dissolved in a suitable solvent and further diluted to avoid matrix interference. The diluted samples were analyzed by reversed-phase chromatography, coupled to a UV detector followed by a triple quadrupole mass spectrometer, used in the multiple reaction monitoring mode. The UV signal was utilized for the quantification of samples containing high levels of CBD, while the mass spectrometer was used for low levels of THC and other minor cannabinoids. This allowed us to meet the required sensitivity for THC while significantly expanding the range of analyzed CBD, all within an 8-min long chromatographic run. The samples were further quantified using calibration in solvent, the approach was validated, and the validation criteria were met for all matrices except for two (i.e., emulsions and gels). The lower limit of quantification for THC was 0.5 μg/g in gummies, 1.0 μg/g in oils, ointments and liquids, and 5.0 μg/g in plant material. CBD was analyzed in the range of 0.5–60,000 μg/g in gummies, 1–120,000 μg/g in oils, ointments and liquids, and 5–300,000 μg/g in plant material. The developed method was used for the analysis of thirteen real products with a wide range of CBD content, with positive THC findings in twelve of them.
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