Deep eutectic solvents as a green alternative to organic solvents for fi-cyclodextrin pseudo-stationary phase in capillary electrophoresis

fi-cyclodextrin (fi-CD), as an important pseudo-stationary phase (PSP) in capillary electrophoresis (CE), frequently confronts challenges stemming from its limited water solubility, particularly when high concentrations are required for resolving complex analytes. Traditionally, researchers often resort to the use of (toxic) organic solvents to enhance the solubility of fi-CD, establishing non-aqueous capillary electrophoresis (NACE) for specific separations. However, such practices are hazardous to health and run counter to the principles of green analytical chemistry. In this study, we demonstrate a deep eutectic solvent (DES), Proline:Urea (PU), as a promising alternative to conventional organic solvents for fi-CD-based CE separations. The DES exhibits a solubility of up to 30% for fi-CD, a significant improvement compared to the 1.8% solubility in the aqueous phase. Utilizing this DES-type separation medium, we achieved simultaneous baseline separation of a complex analyte composed of eight structurally similar naphthoic acid derivatives. Furthermore, we conducted a systematic comparison of fi-CD's performance in aqueous CE buffers, organic solvents, and DESs, highlighting the superiority of this novel and environmentally friendly CE separation medium.