Song Xue, Sihui Ding, Haoxiang Meng, Qing Wu, Zanhao Huang, Qi Zhang
Deep eutectic solvents (DESs) have recently emerged as promising alternatives to conventional separation media in capillary electrophoresis (CE). However, nearly all existing studies have confined DESs to the role of minor additives, with their application as primary separation media remaining largely unexplored. In this work, we investigated the feasibility of employing a DES, Proline:Urea (PU), as the primary separation medium in electrokinetic chromatography (EKC), with a particular focus on its compatibility with cyclodextrins (CDs), one of the most important classes of pseudo-stationary phases in CE. The results showed that PU exhibited excellent solubility for all three native and five derivatized CDs tested, with a particularly significant enhancement (2 to 16 times higher) in the solubility of native CDs compared to water. More importantly, the host-guest properties (mainly the hydrophobic effects) of these CDs were well-preserved in the DES, enabling excellent separations of 3 groups of complex samples, covering 8 anions, 4 cations, and 8 neutrals. By contrast, these separations could not be achieved under conventional aqueous CD-EKC conditions. These findings demonstrate the significant potential of DESs as primary separation media for addressing specific challenges in conventional CE while providing a more sustainable separation strategy.