Nishi H, Nakamura K, Nakai H, Sato T
Analytical Research Laboratory, Tanabe Seiyaku Company, Ltd., Osaka, Japan.
Anal Chem. 1995 Jul 15;67(14):2334-41. doi: 10.1021/ac00110a003.
Chondroitin sulfate C (sodium salt) and heparin (sodium salt), which are both mucopolysaccharides and natural components, have been employed as chiral selectors in electrokinetic chromatography (EKC) for the separation of enantiomers of drugs. These additives are charged, linear, sulfated polysaccharides having large mass. Ionic and hydrophobic interactions are probably the bases for the separation. Among tested drugs that are electrically neutral or basic, trimetoquinol, diltiazem, and their related compounds were successfully enantioseparated by EKC with mucopolysaccharides, especially with chondroitin sulfate C. The choices of pH and the concentration of mucopolysaccharides were found to be important for improvement of enantioselectivity. The acidic buffer solutions were effective for enantioseparation of the solutes in the chondroitin sulfate C system, although no migration of the basic drugs was observed in the heparin system. The results were compared with the enantiomeric separation by EKC with dextran sulfate (sodium salt). The method using chondroitin sulfate C was successfully applied to the optical purity testing of the drug substances.
硫酸软骨素C（钠盐）和肝素（钠盐）均为粘多糖且是天然成分，已被用作电动色谱（EKC）中的手性选择剂用于分离药物对映体。这些添加剂是带电荷的、线性的、具有较大质量的硫酸化多糖。离子相互作用和疏水相互作用可能是分离的基础。在电中性或碱性的受试药物中，曲美托喹诺、地尔硫䓬及其相关化合物通过EKC与粘多糖，特别是与硫酸软骨素C成功实现了对映体分离。发现pH值和粘多糖浓度的选择对于提高对映选择性很重要。酸性缓冲溶液对于硫酸软骨素C系统中溶质的对映体分离有效，尽管在肝素系统中未观察到碱性药物的迁移。将结果与用硫酸葡聚糖（钠盐）通过EKC进行对映体分离的结果进行了比较。使用硫酸软骨素C的方法成功应用于药物原料的光学纯度检测。
