Enantiomeric separation of chiral dipeptides by CE‐ESI‐MS employing a partial filling technique with chiral crown ether

Abstract

Enantiomer of chiral dipeptides were separated by CE-ESI-MS in a bare fused-silica capillary using (1)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (18C 6 H 4 ) as the chiral selector. As 18C 6 H 4 is a kind of nonvolatile chiral selector, in order to prevent from 18C 6 H 4 into the ion-source of CE-ESI-MS, a partial filling technique was employed in this study. Some dipeptides with one chiral center or two chiral centers, such as DL-Leu-DL-Leu, D-Ala-D-Ala and L-Ala-L-Ala, Gly-D-Phe and Gly-L-Phe were used to evaluate this CE-ESI-MS system. Optimized conditions were achivevd with 2.0 mol/L acetic acid (pH 2.15) as the running electrolyte, 5 mM 18C 6 H 4 in 3.0 mol/L acetic acid (pH 2.00) was injected hydrodynamically (50 mbar for 960 s) before sample injection. In total 7.5 mM acetic acid in 80% v/v methanol-water was used as the sheath liquid, and 20 kV applied voltage was used. Under the optimum conditions, these dipeptides were separated and detected. LODs (defined as S/N 5 3) of this method were 0.20, 0.10, 0.05 and 0.10 mmol/L for D-Ala-D-Ala, L-Ala-L-Ala, DL-Leu-DL-Leu, Gly-L-Phe and Gly-D-Phe, respectively. The RSDs (n 5 7) of the method were 0.68-2.08% for migration times and 2.32-5.24% for peak areas. The proposed method was also successfully applied to the enantioselective analysis of these dipeptides in the spiked serum samples with satisfactory results.

Advances in chiral separations of small peptides by capillary electrophoresis and chromatography

“…Xia et al. used a bare fused‐silica capillary with (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid (18C 6 H 4 ) for resolving dipeptides using CE–ESI‐MS.…”

CE-MS in Drug Analysis and Bioanalysis

“…Nonchiral CE-MS can also be applied to elucidate the structures of impurities previously detected by means of a chiral CE-UV separation [40]. Although the usefulness of CE-MS in performing chiral separations of short peptides has been demonstrated [60], to the best of our knowledge, no complete analytical procedure applied to pharmaceutical QC has been fully validated to date.…”

Capillary electrophoretic enantioseparation of basic drugs using a new single-isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism

“…Most of separations of chiral compounds in CE were achieved by the addition of chiral selectors to the running buffer. To date, cyclodextrins (CDs) , antibiotics , polysaccharides and crown ethers , etc. have been used for the chiral separation of enantiomers by CE.…”