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

• Published in: Electrophoresis 2015-10, Vol.36 (19), p.2442-2450
• Main Authors: Mavroudi, Maria C., Kapnissi-Christodoulou, Constantina P.
• Format: Article
• Language: English
• Subjects: Alanine - chemistry; Amino acid ester-based ionic liquid; Amino acids; Anti-Inflammatory Agents, Non-Steroidal - analysis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; beta-Cyclodextrins - chemistry; Chiral separation; Drugs; Dual separation system; Electrophoresis; Electrophoresis, Capillary - methods; Esters; Ibuprofen; Lactates; Lactates - chemistry; Nonsteroidal anti-inflammatory drugs; Phenylpropionates - analysis; Phenylpropionates - chemistry; Phenylpropionates - isolation & purification; Reproducibility of Results; Separation; Stereoisomerism
• ISSN: 0173-0835; 1522-2683
• DOI: 10.1002/elps.201500143

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‐AlaC4Lac). Parameters, such as concentrations of TM‐β‐CD and l‐AlaC4Lac, 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.