A Metabolomic Approach Applied to a LiquidChromatography Coupled to High-ResolutionTandem Mass Spectrometry Method (HPLC-ESI-HRMS/MS): Towards the ComprehensiveEvaluation of the Chemical Composition ofCannabis Medicinal Extracts

Introduction – Cannabis sativa L. is a powerful medicinal plant and its use has recently increased for the treatment of several pa-thologies. Nonetheless, side effects, like dizziness and hallucinations, and long-term effects concerning memory and cognition,can occur. Most alarming is the lack of a standardised procedure to extract medicinal cannabis. Indeed, each galenical prepara-tion has an unknown chemical composition in terms of cannabinoids and other active principles that depends on the extractionprocedure.Objective – This study aims to highlight the main differences in the chemical composition of Bediol® extracts when the extractionis carried out with either ethyl alcohol or olive oil for various times (0, 60, 120 and 180 min for ethyl alcohol, and 0, 60, 90 and120 min for olive oil).Methodology.Cannabis medicinal extracts (CMEs) were analysed by liquid chromatography coupled to high-resolution tandem mass spec-trometry (LC–MS/MS) using an untargeted metabolomics approach. The data sets were processed by unsupervised multivariateanalysis.Results – Our results suggested that the main difference lies in the ratio of acid to decarboxylated cannabinoids, which dramat-ically influences the pharmacological activity of CMEs. Minor cannabinoids, alkaloids, and amino acids contributing to this differ-ence are also discussed. The main cannabinoids were quantified in each extract applying a recently validated LC–MS and LC-UVmethod.Conclusions – Notwithstanding the use of a standardised starting plant material, great changes are caused by different extractionprocedures. The metabolomics approach is a useful tool for the evaluation of the chemical composition of cannabis extracts.