Van Eeckhaut Ann, Detaevernier Marc Robert, Michotte Yvette
Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Pharmaceutical Institute, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
J Pharm Biomed Anal. 2004 Nov 19;36(4):799-805. doi: 10.1016/j.jpba.2004.08.024.
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.
采用电动色谱法研究了三种中性1,4 - 二氢吡啶（DHP）衍生物（尼莫地平、尼索地平、尼群地平）的分离及对映体同时分离。胆汁盐可实现这些DHP衍生物的非手性分离。对于牛磺酸共轭胆汁盐，观察到尼莫地平和尼索地平开始出现对映体分离。十二烷基硫酸钠的非手性胶束与中性环糊精混合不能实现对映体分离。在pH 5.0条件下，羧甲基-β-环糊精可实现尼索地平和尼莫地平的基线手性分离。缓冲液类型影响手性分离，尤其是对于尼索地平。有机溶剂的加入降低了尼莫地平的对映体拆分度。然而，当向背景电解质中加入甲醇或乙醇时，尼索地平对映体之间的分离度增加。改变温度对尼索地平的对映体拆分度几乎没有影响，而对于尼莫地平，在较低温度下观察到明显改善。使用优化方法，研究了该方法对尼索地平三种可能杂质的选择性。
