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-β-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.
According to the model of Wren and Rowe, the separation between two enantiomers in capillary electrophoresis (CE) decreases if an organic modifier is added to the run buffer containing a neutral ...cyclodextrin (CD) in a concentration below its optimal value in a solvent‐free system. In previous work, however, it was observed that the addition of methanol to the background electrolyte (BGE) containing not charged carboxymethyl‐β‐CD in a concentration below its optimal value, increased the enantioresolution of dimetindene maleate. The enantioresolution decreased when other organic modifiers (ethanol, isopropanol or acetonitrile) were added and/or when other neutral (β‐CD, hydroxypropyl‐β‐CD) or chargeable (carboxyethyl‐β‐ and succinyl‐β‐CD) CDs were used. In this CE study further attempts are made to elucidate the observed phenomena through investigating other basic drugs. The effect of organic modifier and CD concentration on the enantioseparation was studied by means of central composite designs. It is shown that obtaining this increase in enantioresolution depends upon the type of CD, the type of organic modifier, and the structure of the analytes. It was also observed that small differences in the structure of the analytes or the CD could have an influence on the enantioresolution. The addition of methanol also resulted in different effects on the resolution of closely related analytes.
Methanol enhances the enantioresolution of dimetindene enantiomers with carboxymethyl‐β‐cyclodextrin (CMCD) as chiral selector at a concentration below its optimal value. The same effect was observed ...with ethanol (EtOH), although less pronounced. On the other hand, the addition of isopropanol (IP) or acetonitrile (ACN) decreases the enantioseparation. To elucidate the underlying mechanisms of these observed effects, other neutral (β‐CD, hydroxypropyl‐β‐CD, and trimethyl‐β‐CD) as well as chargeable (carboxyethyl‐β‐CD and succinyl‐β‐CD) CD derivatives were also tested with MeOH as organic modifier. It can be concluded that the increased enantioresolution of dimetindene enantiomers was only noted with CMCD as chiral selector and a short‐chain organic modifier containing an alcohol function. The slight deprotonation of CMCD at pH 3.0 was only partly responsible for the high enantioselectivity and the ‘favourable’ effect of MeOH or EtOH. An important feature that can be concluded from these results is that for this particular analyte approximately the same resolution can be obtained with a lower CMCD concentration and the addition of some MeOH, compared to a MeOH free buffer.
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