Chemoselectivity of Normal Phase Stationary Phases Towards the Separation of Cannabinoids

Due to the progress decriminalization of recreational cannabis and the growing interest in hemp and cannabis products, in the last years much effort has been devoted to investigating the biological and pharmacological activity of cannabinoids in order to ensure consumer safety [1]. However, only 20% of natural occurring cannabinoids (or phytocannabinoids) is currently available as a certified reference material and new cannabinoids are continuously being discovered [2]. The purification of cannabinoids, especially from hemp extracts, could be very challenging due to the presence of many components (such as terpenes, waxes, other cannabinoids, etc.) often with similar chemical structure. This points the attention on the need of fast, efficient, and cost-effective methods for the isolation and purification of cannabinoids, especially from plant materials [3,4]. In this field, preparative liquid chromatography (LC), either in batch or in continuous multicolumn countercurrent chromatography (MCC), is the most employed technique for industrial purification of cannabinoids. However, a deeper understanding of the fundamentals of cannabinoids adsorption is required for the selection of the optimal combination of mobile phases and column chemistries. In this work, four 1504 mm polar columns (NH2, Diol, Si and CN) packed with 5 µm particles have been compared, under normal phase (NP) conditions, in terms of retention and selectivity towards the separation of five neutral phytocannabinoids (CBD, CBC, CBG, CBN and Δ9-THC). Results indicate that NP chromatography could be an alternative solution compared to RP chromatography for the separation of this important class of compounds. In addition, this mode seems very promising for the large scale separations of cannabinoids due to fast analysis, low backpressure, high selectivity and high sample solubility.