An LC-MS/MS method for the quantification of cannabinoids in over-the-counter food supplements and exploratory detection of cannabidiol in human sebum as a potential post-administration matrix

Background The commercial availability of cannabidiol (CBD)-based products has increased exponentially, often without adequate regulation, raising concerns about product integrity and consumer safety. The analgesic and anxiolytic properties of CBD occur via the endocannabinoid system, which is also active in the skin, where CBD acts directly on sebum-producing sebocytes. Sebum has shown potential as a non-invasive diagnostic tool for diseases, but its applicability for cannabinoid monitoring remains unexplored. This study aimed to develop and validate an analytical method for the quantification of six cannabinoids in commercial products and to explore its application to human sebum samples. Methods Eight over-the-counter (OTC) products, including oils, tablets, gummies and teas, obtained from the UK market were analysed to quantify cannabidiol (CBD), ∆9-tetrahydrocannabinol (THC), cannabidiolic acid (CBDA) and ∆9-tetrahydrocannabinolic acid (THCA) by liquid chromatography-mass spectrometry (LC-MS/MS). Matrix effects were accounted for by using either an internal standard (IS) or a standard addition approach. Sebum samples from the forehead of participants ( n = 10) following single dose oral or sublingual CBD consumption were analysed to detect CBD, THC, 7-carboxy-cannabidiol (7-COOH-CBD) and 11-nor-9-carboxy-∆9-tetrahydrocannabinol (11-COOH-THC). Results Validation parameters of the six cannabinoids included linearity with R² > 0.99, limits of detection of 0.02–0.34 ng/mL, limits of quantification of 0.07–1.2 ng/mL, recoveries between 82.9% and 116.8%, acceptable repeatability and reproducibility (HorRat < 2.0; %RSD < 20%), and an expanded uncertainty of 25.2% at 95% confidence interval. Consistent with previous studies, product analysis revealed substantial discrepancies (> 36% CBD) between labelled and measured CBD content with all products containing less CBD than declared and no products exceeding the legal total THC limits. Following oral or sublingual CBD consumption at label-declared doses of less than 70 mg in various forms (tablets, oils, tea, coffee, soda and gummies), CBD was detected on the forehead of all ten participants (estimated 0.4 to 92.5 pg/swab). No 7-COOH-CBD, 11-COOH-THC or THC were detected in the sebum samples. Conclusion The proposed LC-MS/MS method demonstrated suitability for the routine monitoring of cannabinoids across various food product types. CBD was also detected in forehead sebum after oral or sublingual consumption of OTC CBD products, supporting further investigation of sebum as a candidate post-administration matrix.