Separation of neutral dihydropyridines and their enantiomers using electrokinetic chromatography.

The separation and simultaneous enantiomeric separation of three neutral 1,4-dihydropyridine (DHP) derivatives (nimodipine, nisoldipine and nitrendipine) was studied using electrokinetic chromatography. Bile salts allowed the non-chiral separation of these DHP derivatives. With the taurine-conjugated bile salts a beginning of enantiomeric separation was observed for nimodipine and nisoldipine. Achiral micelles of sodium dodecyl sulphate mixed with neutral cyclodextrins did not allow enantioseparation. Baseline chiral separation of nisoldipine and nimodipine was obtained with carboxymethyl-beta-cyclodextrin at pH 5.0. The buffer type affected the chiral separation, especially in the case of nisoldipine. The addition of organic solvent decreased the enantioresolution of nimodipine. However, the resolution between the nisoldipine enantiomers was increased when methanol or ethanol were added to the background electrolyte. Varying the temperature had almost no effect on the enantioresolution of nisoldipine, whereas with nimodipine a clear improvement at lower temperatures was observed. Using the optimised method, the selectivity of this method was investigated for three possible impurities of nisoldipine.