Quantification of Cannabinoids in Cannabis Oil Using GC/MS: Method Development, Validation, and Application to Commercially Available Preparations in Argentina

Abstract

Abstract The medicinal use of cannabis oil is increasing all over the world. Few analytical methods for the quantification of cannabinoids have been validated using internationally accredited guidelines. This work describes the development and validation of a selective and sensitive gas chromatography-mass spectrometry method for the qualitative analysis of the main cannabinoids, namely cannabidiolic acid, tetrahydrocannabinolic acid, cannabigerol, and cannabichromene as well as quantitative determination of cannabidiol, Δ9-tetrahydrocannabinol, and cannabinol, present in cannabis oils. The method was fully validated according to Food and Drug Administration and International Conference on Harmonization guidelines. A linear range of 0.1–30 μg/mL was obtained for CBD and Δ9-THC and 0.034–11.7 μg/mL for CBN, presenting determination coefficients above 0.99. The lower limits of quantification ranged from 0.034 to 0.1 μg/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 3.9–13.8 and 4.7–14.1%, respectively. Extraction efficiency at lower limits of quantification was 95–103%. Verification of method validity was performed with authentic cannabis oil samples. To our knowledge, this is the first method available in Argentina, validated according to international guidelines, for quantification of CBD, Δ9-THC, and CBN in cannabis oil. The primary application of this method is to differentiate between cannabis oils with high or low content of Δ9-THC, CBD, or mixed Δ9-THC/CBD. This is of fundamental importance for the patient and so that the physicians can carry out a suitable therapy.