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.