Liquid Chromatography for Cannabinoids Separations: State of the Art and Future Perspectives

In the last years, several countries have legalized cannabis for medical purposes and/or for recrea5onal use. Therefore, the demand for accurate analy5cal methods, able to provide a detailed characteriza5on of cannabis samples and extracts, and fast, efficient, and cost-effec5ve methods for the isola5on of cannabinoids has increased. In this context, HPLC is emerging as the golden standard for rou5ne potency tes5ng analysis and for prepara5ve purposes. However, method development for the separa5on of cannabinoids is s5ll in its early stages. Indeed, almost the totality of the available LC methods is based on the classical achiral reversed-phase liquid chromatography (with C18 sta5onary phases and acetonitrile as organic modifier), where the resolu5on of species with very similar chemical structures (such as the Δ9-THC/Δ8-THC pair) can be par5cularly challenging. Moreover, only a few fundamental studies about reten5on and adsorp5on of cannabinoids have been performed. As a consequence, the development of separa5on processes is s5ll based on trial-and-error strategy, cons5tu5ng an important limita5on, especially from the industrial viewpoint. Thus, the need of exploring novel adsorbents, different elu5on modes, various experimental condi5ons, and possibly to exploit fundamental informa5on for the successful method development. These studies will contribute to obtain different selec5vity and more and more efficient runs, if compared to the classical methods, being able to overcome (almost) all the observed limita5ons.