Improved chiral separations of basic compounds in capillary electrophoresis using .beta.-cyclodextrin and tetraalkylammonium reagents

Abstract

Approaches to improve resolution in chiral separation of several basic pharmaceutical compounds by capillary electrophoresis (CE) via a cyclodextrin (CD) inclusion complexation are described. Tetraalkylammonium reagents, including long-chain cationic surfactants and short-chain alkylammonium hydroxides, are examined for controlling the electroosmotic flow in order to improve resolution of the cationic enantiomers. In this regard, short-chain tetraalkylammonium cations (such as tetrabutylammonium and tetramethylammonium are more effective. First, the short-chain tetraalkylammonium cations can be used at much higher concentrations than the long-chain cationic surfactants, which form micelles in the few millimolar concentration range. As a result, a better capillary wall coverage is provided with the short-chain reagents, which leads to reduction or reversal of the direction of the electroosmotic flow at the acidic pH 2.5. Second, the short-chain tetraalkylammonium cations are relatively less hydrophobic and less likely to occupy the hydrophobic cavity of beta-CD than the long-chain cationic surfactants, leaving the enantioselective interaction sites more available for the analytes. The presence of these tetraalkylammonium cations was essential in many chiral separations that were reportedly not achieved by using the buffer electrolytes containing only the beta-CD as a chiral selector. In addition, a mechanism of chiral recognition by beta-CD for a group of stereoisomers is discussed.

Separation and determination of norepinephrine, epinephrine and isoprinaline enantiomers by capillary electrophoresis in pharmaceutical formulation and human serum

“…The validation of this method for the quantitation of isoprenaline aerosol and to the analysis of serum samples spiked norepinephrine and epinephrine was performed. Compared with the previous methods [10][11][12][13][14][15][16][17][18], the merit of this work was used to analyze enantiomers of norepinephrine, epinephrine or isoprinaline in pharmaceutical formulation and human serum. The results indicated the proposed method represents good selectivity, precision and accuracy.…”

“…Above 30 mM, the enantiomeric separation of NE or EP could not be improved and the migration time increased. Many papers [10,13,20] reported that using dual CD system could obtain higher enantiomeric resolutions. Therefore, in our work, 5 mM of ␤-CD, Me-␤-CD or DM-␤-CD was added to the running buffer containing 30 mM HP-␤-CD, respectively.…”

“…A number of analytical methods have been reported to determine EP, NE and isoprenaline (IP) enantiomers [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Among them, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) are the most widely used separation techniques.…”

“…CE with the direct method using ␤-cyclodextrin (␤-CD) or derivatized-CD as chiral selectors was reported to be effective for enantiomer separations of NE, EP and IP. Quang and Khaledi [10] reported the use of ␤-CD and tetraalkylammonium for the separation of NE, EP and IP enantiomers. However, only partial separation was obtained for NE and EP.…”

NMR Spectroscopic Analysis on the Chiral Recognition of Noradrenaline by β-Cyclodextrin ( β-CD) and Carboxymethyl- β-cyclodextrin (CM- β-CD)

“…These data are also in good accordance with the reported experimental data in HPLC 12 or CE. 13,20 It supports that CM-β-CD is a better chiral selector for NA enantiomers comparing with β-CD.…”