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

The retention order of the enantiomers of clevedipine (solute no 1), a shor tacting blood pressure reducer, was controlled by type of organic modifier With l-propanol as mobile phase modifier the (R)-form eluted first and by u sing methanal, the (S)-form was first to elute. These effects could also be seen for the hydrolysed analogue to clevedipine, an acid (solute no 2). Th e reversal of retention order was then obtained when l-propanol was replace d by acetonitrile An oxidized analogue to clevedipine, a pyridine (solute n o 3), was also tested regarding reversal of retention order of in enantiome rs. In this case the retention order could not be controlled by type of org anic modifier. The influence of the mobile phase burier pH on enantioselective retention w as 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 ai di fferent 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.