Abstract:The present study investigates the utilization of a supramolecular deep eutectic solvent (SUPRADES), consisting of sulfated‐β‐cyclodextrin (S‐β‐CD) and citric acid (CA), as a chiral selector (CS) in capillary electrophoresis for the enantiomeric separation of nefopam (NEF) and five cathinone derivatives (3‐methylmethcathinone [3‐MMC], 4‐methylmethcathinone [4‐MMC], 3,4‐dimethylmethcathinone [3,4‐DMMC], 4‐methylethcathinone [4‐MEC], and 3,4‐methylendioxycathinone [MDMC]). A significant improvement in enantiomeric separation of the target analytes was observed upon the addition of S‐β‐CD‐CA to the background electrolyte (BGE), leading to a baseline separation of all analytes. In particular, the optimum percentage of S‐β‐CD‐CA, added to the BGE, was determined to be 0.075% v/v for NEF (Rs = 1.5) and 0.050% v/v for three out of five cathinone derivatives (Rs = 1.5, 1.6, and 2.4 for 3‐MMC, 4‐MEC, and 3,4‐DMMC, respectively). In the case of 4‐MMC and MDMC, a higher percentage of the CS, equal to 0.075% and 0.10% v/v, respectively, was required to achieve baseline separation (Rs = 1.5, 1.9 for MDMC and 4‐MMC, respectively). The outcomes of the present study highlight the potential effectiveness of using SUPRADES as a CS in electrophoretic enantioseparations.