Gyllenhaal Olle, Stefansson Morgan
Analytical Development, Pharmaceutical and Analytical R&D, AstraZeneca R&D Mölndal, S 431 83 Mölndal, Sweden.
J Pharm Biomed Anal. 2008 Apr 14;46(5):860-3. doi: 10.1016/j.jpba.2007.03.009. Epub 2007 Mar 14.
Enantiomeric separations of four 2-substituted propionic acid drugs and two related acids have been studied using normal phase liquid chromatography with amylose (tris 3,5-dimethylphenylcarbamate) coated on silica as support (Chiralpak AD). At standard conditions (i.e. flow-rate, 1.0 ml/min; column temperature, 30 degrees C) the elution order can be reversed when the polar alcohol modifier in isohexane, 2-propanol, is replaced by methanol/ethanol 2:1. This is the case for ibuprofen with 2.5% (v/v) alcohol and for mandelic acid with 10% (v/v) alcohol using synthetic mixtures with unequal proportions of the respective enantiomer. Thermodynamic studies in the range 10-45 degrees C on retention and selectivity of ibuprofen and mandelic acid gave both linear and curved plots. These results stress the importance of investigating enantiomer elution order during the development of enantioselective methods when both old and new CSPs are evaluated. One should also keep in mind that reversal can take place for rather common analytes in well established enantioselective chromatographic systems.
使用涂覆有直链淀粉（三（3,5 - 二甲基苯基氨基甲酸酯））的硅胶作为固定相（Chiralpak AD）的正相液相色谱法，研究了四种2 - 取代丙酸类药物和两种相关酸的对映体分离。在标准条件下（即流速1.0 ml/min；柱温30℃），当异己烷中的极性醇改性剂2 - 丙醇被甲醇/乙醇2:1取代时，洗脱顺序可能会颠倒。对于含有2.5%（v/v）醇的布洛芬以及含有10%（v/v）醇的扁桃酸，使用各自对映体比例不等的合成混合物时就是这种情况。在10 - 45℃范围内对布洛芬和扁桃酸的保留和选择性进行的热力学研究给出了线性和曲线型的图谱。这些结果强调了在评估新旧手性固定相时，在对映体选择性方法开发过程中研究对映体洗脱顺序的重要性。人们还应记住，在成熟的对映体选择性色谱系统中，相当常见的分析物可能会发生洗脱顺序的颠倒。
