Combined use of l‐alanine tert butyl ester lactate and trimethyl‐β‐cyclodextrin for the enantiomeric separations of 2‐arylpropionic acids nonsteroidal anti‐inflammatory drugs

Abstract

In this study, a new CE method, employing a binary system of trimethyl-β-CD (TM-β-CD) and a chiral amino acid ester-based ionic liquid (AAIL), was developed for the chiral separation of seven 2-arylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs). In particular, the enantioseparation of ibuprofen, ketoprofen, carprofen, indoprofen, flurbiprofen, naproxen, and fenoprofen was improved significantly by supporting the BGE with the chiral AAIL l-alanine tert butyl ester lactate (l-AlaC4 Lac). Parameters, such as concentrations of TM-β-CD and l-AlaC4 Lac, and buffer pH, were systematically examined in order to optimize the chiral separation of each NSAID. It was observed that the addition of the AAIL into the BGE improved both resolution and efficiency significantly. After optimization of separation conditions, baseline separation (Rs >1.5) of five of the analytes was achieved in less than 11 min, while the resolution of ibuprofen and flurbiprofen was approximately 1.2. The optimized enantioseparation conditions for all analytes involve a BGE of 5 mM sodium acetate/acetic acid (pH 5.0), an applied voltage of 30 kV, and a temperature of 20°C. In addition, the results obtained by computing the %-RSD values of the EOF and the two enantiomer peaks, demonstrated excellent run-to-run, batch-to-batch, and day-to-day reproducibilities.

Biological Activity of Ionic Liquids and Their Application in Pharmaceutics and Medicine

“…The IL coating provided improved resolution and precluded absorption of the substances on the capillary wall . Usage of imidazolium-based ILs as mobile phase additives in the reversed-phase liquid chromatography enhanced separation of basic drugs by alleviating the issue of broad chromatographic peaks, which arose through interactions of the positively charged drugs with free silanol groups of the reverse phase. , In addition, employment of chiral ILs as electrolyte additives during electrophoresis allowed separating enantiomers of various active pharmaceutical ingredients. − Similarly, an IL-functionalized β-dextrin was successfully used as chiral selector in capillary electrophoresis . A fluorescence technique based on interactions of enantiomers with optically active ILs was proposed for establishing enantiomeric composition of drugs …”

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

“…CILs have attracted much attention for several applications, such as chiral solvents, asymmetric synthesis, a, recently, chiral CE for the separation of enantiomers. CILs are commonly used as chiral selectors, chiral ligands, and in the BGE, as listed in Table 2 [114–154]. ACILs such as the ones based on alkylpyridinium, alkyl imidazolium, and tetraalkylammonium are also used in CE separation with combinations of β‐CD derivatives and furnish a favored interaction with enantiomers.…”

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…Recently, in order to further improve its enantioseparation capability, TM‐β‐CD was used in combination with the chiral IL l ‐alanine tert butyl ester lactate ( l ‐AlaC 4 Lac) . The synergistic effect on the enantioseparation of 2‐arylpropionic acids nonsteroidal anti‐inflammatory drugs was investigated.…”