Addition of organic modifiers to control retention order of enantiomers of dihydropyridines on chiral-AGP

Summary

The retention order of the enantiomers of clevedipine (solute no 1), a shortacting blood pressure reducer, was controlled by type of organic modifier. With 1-propanol as, mobile phase modifier the (R)-form eluted first and by using methanol, the (S)-form was first to elute. These effects could also be seen for the hydrolysed analogue, to clevedipine, an acid (solute no 2). The reversal of retention order was then obtained when 1-propanol was replaced by acetonitrile. An oxidized analogue to clevedipine, a pyridine (solute no 3), was also tested regarding reversal of retention order of its enantiomers. In this case the retention order could not be controlled by type of organic modifier.

The influence of the mobile phase buffer pH on enantioselective retention was also studied for the three substances. For clevidipine and the oxidized analogue, a high mobile phase pH favored enantioselective resolution while the opposite result was obtained for the hydrolysed analogue.

Temperature studies were also performed, and enthalpies and entropies at different mobile phase pH:s using different organic modifiers were calculated, in order to promote an understanding of the thermodynamic driving forces for retention in the systems.

Optimized chromatographic systems were used to determine less than 0.1% of an enantiomeric impurity in (R)- and (S)-clevidipine.