Fradi Ines, Servais Anne-Catherine, Pedrini Matteo, Chiap Patrice, Iványi Róbert, Crommen Jacques, Fillet Marianne
Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liège, Liège, Belgium.
Electrophoresis. 2006 Sep;27(17):3434-42. doi: 10.1002/elps.200500643.
The enantiomeric separation of a series of acidic pharmaceuticals (mostly nonsteroidal anti-inflammatory drugs) has been investigated in NACE systems using single-isomer amino beta-CD derivatives. The first part of this study consisted of the selection of the basic experimental conditions to separate efficiently the enantiomers of acidic drugs. Several parameters, such as the nature of the ionic BGE components, were studied and a methanolic solution of ammonium acetate containing the cationic CD was selected as BGE. A D-optimal design with 20 experimental points was then applied and the nature and concentration of the CD were found to have a significant effect on the enantiomeric resolution for all studied compounds. Resolution (R(s)) values were always higher with 6-monodeoxy-6-mono(3-hydroxy)propylamino-beta-CD (PA-beta-CD) compared to those obtained with 6-monodeoxy-6-mono(2-hydroxy)propylamino-beta-CD (IPA-beta-CD). However, the latter led to shorter migration times. Generic NACE conditions were then selected by means of the multivariate approach in order to obtain the highest R(s) values in a minimum amount of time. Finally, dependence of separation selectivity, resolution, as well as mobility difference on chiral selector concentration was discussed and binding constants with PA-beta-CD were estimated for the two enantiomers of one of the model compounds, suprofen in these NACE systems.
使用单异构体氨基β-环糊精衍生物，在非水毛细管电泳（NACE）体系中研究了一系列酸性药物（主要是非甾体抗炎药）的对映体分离。本研究的第一部分包括选择能有效分离酸性药物对映体的基本实验条件。研究了几个参数，如离子背景电解质（BGE）组分的性质，并选择了含有阳离子环糊精的醋酸铵甲醇溶液作为BGE。然后应用了具有20个实验点的D-最优设计，发现环糊精的性质和浓度对所有研究化合物的对映体拆分有显著影响。与使用6-单脱氧-6-单（2-羟基）丙基氨基-β-环糊精（IPA-β-CD）相比，使用6-单脱氧-6-单（3-羟基）丙基氨基-β-环糊精（PA-β-CD）时的拆分度（R(s)）值总是更高。然而，后者导致迁移时间更短。然后通过多变量方法选择通用的NACE条件，以便在最短时间内获得最高的R(s)值。最后，讨论了分离选择性、拆分度以及迁移率差异对手性选择剂浓度的依赖性，并在这些NACE体系中估算了模型化合物舒洛芬的两种对映体与PA-β-CD的结合常数。
