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在非水毛细管电泳中使用七(2,3-二-O-甲基-6-O-磺基)-β-环糊精与樟脑磺酸钾联用对碱性化合物进行对映体分离:通过实验设计进行优化

Enantiomeric separation of basic compounds using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin in combination with potassium camphorsulfonate in nonaqueous capillary electrophoresis: optimization by means of an experimental design.

作者信息

Servais Anne-Catherine, Fillet Marianne, Chiap Patrice, Dewé Walthère, Hubert Philippe, Crommen Jacques

机构信息

Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liège, Liège, Belgium.

出版信息

Electrophoresis. 2004 Aug;25(16):2701-10. doi: 10.1002/elps.200405962.

DOI:10.1002/elps.200405962
PMID:15352001
Abstract

The enantiomeric separation of a series of basic pharmaceuticals (beta-blockers, local anesthetics, sympathomimetics) has been investigated in nonaqueous capillary electrophoresis (NACE) systems using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) in combination with potassium camphorsulfonate (camphorSO3-). For this purpose, a face-centered central composite design with 11 experimental points was applied. The effect of the concentrations of HDMS-beta-CD and camphorSO3- on enantioresolution was statistically evaluated and depended largely on the considered analyte. The presence of camphorSO3- was found to be particularly useful for the enantioseparation of compounds with high affinity for the anionic CD. CamphorSO3- seems to act as a competitor, reducing the affinity for the CD, probably by ion-pair formation with these analytes. For compounds with lower affinity for HDMS-beta-CD, the combination of camphorSO3- and the CD appeared to have a favorable effect on enantioresolution only if the optimal CD concentration could be reached. On the other hand, for compounds characterized by a very low affinity for the anionic CD, the association of camphorSO3- and HDMS-beta-CD is always unfavorable. Finally, experimental conditions were selected by means of the multivariate approach in order to obtain the highest resolution (Rs) value for each studied compound.

摘要

在非水毛细管电泳(NACE)系统中,使用七(2,3-二-O-甲基-6-O-磺基)-β-环糊精(HDMS-β-CD)与樟脑磺酸钾(樟脑SO3-)的组合,研究了一系列碱性药物(β-受体阻滞剂、局部麻醉剂、拟交感神经药)的对映体分离。为此,应用了具有11个实验点的面心中央复合设计。统计评估了HDMS-β-CD和樟脑SO3-浓度对对映体拆分的影响,其在很大程度上取决于所考虑的分析物。发现樟脑SO3-的存在对于与阴离子型环糊精具有高亲和力的化合物的对映体分离特别有用。樟脑SO3-似乎起到了竞争剂的作用,可能通过与这些分析物形成离子对来降低对环糊精的亲和力。对于对HDMS-β-CD亲和力较低的化合物,只有在达到最佳环糊精浓度时,樟脑SO3-与环糊精的组合才对对映体拆分有有利影响。另一方面,对于对阴离子型环糊精亲和力非常低的化合物,樟脑SO3-与HDMS-β-CD的结合总是不利的。最后,通过多变量方法选择实验条件,以便为每个研究的化合物获得最高的分辨率(Rs)值。

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