Leandros A. Skaltsounis

Introduction Cannabis sativa L. is attracting worldwide attention due to various health‐promoting effects. Extraction solvent type is critical for the recovery of bioactive compounds from the plant, especially cannabinoids. However, the choice of solvent is varied and not adequately warranted elsewhere, causing confusion in involved fields. Objective The present work aimed to investigate the effect of extraction solvent on C. sativa (hemp) with regard to cannabinoid recovery and phytochemical profile of the extracts, considering most of the related solvents. Methodology The majority of solvents reported for C. sativa ( n = 14) were compared using a representative hemp pool. Quantitative results for major and minor cannabinoids were rapidly and reliably obtained using ultrahigh‐performance liquid chromatography coupled with photodiode array detection (UPLC‐PDA). In parallel, high‐performance thin‐layer chromatographic (HPTLC) fingerprinting was employed, involving less toxic mobile phase than in relevant reports. Various derivatisation schemes were applied for more comprehensive comparison of extracts. Results Differential selectivity towards cannabinoids was observed among solvents. MeOH was found particularly efficient for most cannabinoids, in addition to solvent systems such as n ‐Hex/EtOH 70:30 and ACN/EtOH 80:20, while EtOH was generally inferior. For tetrahydrocannabinol (THC)‐type compounds, EtOAc and n ‐Hex/EtOAc 60:40 outperformed n ‐Hex, despite its use in the official EU method. Solvents that tend to extract more lipids or more polar compounds were revealed based on HPTLC results. Conclusion Combining the observations from UPLC quantitation and HPTLC fingerprinting, this work allowed comprehensive evaluation of extraction solvents, in view of robust quality assessment and maximised utilisation of C. sativa .