Synergistic enantioseparation systems with either cyclodextrins or cyclofructans and L‐alanineTertbutyl ester lactate

Abstract

The combined use of chiral ionic liquids (CILs) and conventional chiral selectors (CSs) in CE, to establish a synergistic system, has proven to be an effective approach for the separation of enantiomeric pairs. In this study, a new CE method was developed, employing a binary system of a CS, either a cyclodextrin (CD) or a cyclofructan (CF), and a chiral amino acid ester‐based ionic liquid (AAIL), for the chiral separation of four basic, acidic and zwitterionic drug compounds. In particular, the enantioseparation of two anticoagulants, warfarin (WAR) and coumachlor (COU), a non‐opioid analgesic, nefopam (NEF) and a third‐generation antihistamine, fexofenadine (FXD), was examined, by supporting the BGE with a CS and the chiral AAIL L‐alanine tert butyl ester lactate (L‐AlaC4Lac). Parameters, such as the type of the CS, the concentration of both the CS and L‐AlaC4Lac, and the BGE pH, were methodically examined in order to optimize the chiral separation of each analyte. It was observed that, in some cases, the addition of the AAIL into the BGE improved both resolution (Rs) and efficiency (N) significantly. In other cases, the synergistic effect enabled baseline separation of analyte enantiomers, at a much lower concentration of the CS. Finally, after optimization of separation conditions, baseline separations (Rs>1.5) of all four analytes were achieved in less than 5 min.

From capillaries to microchips, green electrophoretic features for enantiomeric separations: A decade review (2013–2022)

“…Another alternative to achiral ILs with combinations of -CD derivatives is ILs associated to cyclofructans (CFs). For example, these systems have been successfully applied for the chiral separation of drug compounds [126,137].…”

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods

“…The use of additives to enhance/modulate CD-driven chiral separations has been known for a long time, and CD-modified micellar electrokinetic chromatography (CD-MEKC) [ 97 , 98 ] as well as CD-modified microemulsion electrokinetic chromatography (CD-MEEKC) [ 99 ] can be included in this strategy. Recently chiral ILs have been the focus of an intense interest as additives for their synergistic effect on CD-driven enantioseparations [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 ], and in some instances, for functionalization of the CDs [ 113 , 114 ]. The synergistic effect on the chiral separation by CDs has recently been reported by the utilization of eutectic solvents [ 115 , 116 , 117 ].…”

Chiral Capillary Electrokinetic Chromatography: Principle and Applications, Detection and Identification, Design of Experiment, and Exploration of Chiral Recognition Using Molecular Modeling

“…A dual CDs CS system of sulfobutyl-ether-β-CD and native γ-CD resulted in a good enantioseparation of lansoprazole and rabeprazole [ 88 ]. Nicolaou et al [ 89 ] developed two dual CS systems to separate the enantiomers of warfarin, coumachlor, nefopam, and fexofenadine using either CD or cyclofructan with the CIL L-alanine tert butyl ester lactate. The addition of the CIL to the BGE was found to improve the resolution.…”