Enantiomer Separation Of1,4-Dihydropyridines By Supercrtical Fluid Chromatography

Chiral1,4-Dihydropyridines (DHPs) have been widely used in anti-hypertension. The enantiomers of chiral drugs in organism often show different pharmacological actions. Therefor to study enantiomer separation is of great importance to improving the safety of chiral medicines. Eleven1,4-DHPs (nicardipine hydrochloride, nisoldipine, nitrendipine, nimodipine, felodipine, cilnidipine, lacidipine, azelnidipine, manidipine hydrochloride, pranidipine, lercanidipine hydrochloride) were separated by supercritical fluid chromatography (SFC) with supercritical CO2added different type and concentration of modifiers as the mobile phase (methanol, ethanol,2-propanol, acetonitrile;2%-26%). The effect of different chiral stationary phases (Sino-Chiral OJ, Chiralcel OD, Chiralpak IB), column temperature (29-41℃) and back pressure (130-170bar) on the separation was also investigated.With the results of chiral separation of111,4-DHPs on three different CSPs, the optimal separation condition of each compounds was selected.10DHPs were separated except felodipine, nicardipine hydrochloride, nisoldipine, nitrendipine, nimodipine, cilnidipine, Lacidipine, azelnidipine, manidipine hydrochlorid and pranidipine obtained optimal separation on Sino-Chiral OJ column; lercanidipine hydrochloride got optimal separation on Chiralcel OD-H column.7DHPs were completely separated and3DHPs were partially separated on Sino-Chiral OJ column which has advantages of chiral recognition over Chiralpak IB column and Chiralcel OD-H column. Sino-Chiral OJ and Chiralpak IB column has better performance in separation speed over Chiralcel OD-H column.It is inevitable to add a proportion of modifier to the mobile phase, or the compounds are very difficult to be eluted. When using the different modifier of the same concentration, capacity factor of drugs on three different chiral columns decreased in order of2-propanol, ethanol, methanol. The changes of separation factor and resolution were not uniform. On Sino-Chiral OJ column, separation factor and resolution had complicated change depending on the change of modifier type and we could not conclude a law. On Chiralcel OD-H column, separation factor and resolution decreased in order of2-propanol, methanol, and ethanol. On Chiralpak IB column, separation factor and resolution decreased in order of2-propanol, ethanol, and methanol. Every compound had its own best modifier conditions. When using the same modifier, as the concentration increased, capacity factor and resolution gradually reduced. The separation factor stabilized in relative range.On Sino-Chiral OJ column, separation factor stabilized in relative range. Capacity factor and resolution presented complicated change depending on temperature and it’s difficult to find a unified rule. The isoenantioselective temperature of Nicardipine hydrochloride, Nimodipine and Pranidipine were381.9K,348.8K and392.1K, which were above the range of temperature assayed. The enantiomeric separation was an "enthalpy driven" process and the separation factor decreased as the temperature increased.On Sino-Chiral OJ column, as the pressure increased, the capacity factor of DHPs enantiomers basically decreased. The separation factor kept within a certain range. The change of the resolution was complicated. Nitrendipine, felodipine and lacidipine didn’t separate with2%,3%and4%methanol respectively unless the backpressure rose to170bar.