Optimization of the separation of enantiomers of basic drugs. Retention mechanisms and dynamic modification of the chiral bonding properties on an alpha 1-acid glycoprotein column.

The chromatographic properties of 29 basic drugs were studied by varying the pH and the concentration of inorganic ions in the mobile phase. It was observed that the chromatographic performance of most hydrophobic basic drug compounds could be strongly enhanced by decreasing the pH in the mobile phase from 7 to 4-6. The enantioselectivity increased and a much faster resolution was obtained. The results indicate that ion exchange and ion-pair distribution may be involved in the retention process of cationic drug enantiomers. Increasing the concentration of acetate and phosphate increases the retention of the enantiomers of the drug compounds. The relative contribution of the two retention processes can be affected by the pH and the nature and the concentration of the ions in the mobile phase. Decreasing the pH reduces the influence of the ion-exchange process since the negative charge of the protein is decreased. The enantioselectivity is also greatly affected by increasing salt concentration.