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Capillary electrokinetic chromatography for chiral separation of potential SARS-CoV-2 3CL protease inhibitors
Electrophoresis ( IF 2.9 ) Pub Date : 2024-01-15 , DOI: 10.1002/elps.202300178
Lucile Brier 1 , Christophe Furman 2 , Julie Charton 1 , Benoit Deprez 1 , Emmanuelle Lipka 2
Affiliation  

In this work, a capillary electrophoresis method was developed as a quality control tool to determine the enantiomeric purity of a series of five chiral compounds evaluated as potential severe acute respiratory syndrome coronavirus 2 3CL protease inhibitors. The first cyclodextrin tested, that is, highly sulfated-β-cyclodextrin, at 6% (m/v) in a 25 mM phosphate buffer, using a capillary dynamically coated with polyethylene oxide, at an applied voltage of 15 kV and a temperature of 25°C, was found to successfully separate the five derivatives. The limits of detection and quantification were calculated together with the greenness score of the method in order to evaluate the method in terms of analytical and environmental performance. In addition, it is noteworthy that simultaneously high-performance liquid chromatography separation of the enantiomers of the same compounds with two different columns, the amylose tris(3,5-dimethylphenylcarbamate)-coated and the cellulose tris(3,5-dichlorophenylcarbamate)-immobilized on silica stationary phases, was studied. Neither the former stationary phase nor the latter was able to separate all derivatives in a mobile phase consisting of n-heptane/propan-2-ol 80/20 (v/v).

中文翻译:

毛细管电动色谱法用于手性分离潜在的 SARS-CoV-2 3CL 蛋白酶抑制剂

在这项工作中,开发了一种毛细管电泳方法作为质量控制工具,用于测定一系列五种手性化合物的对映体纯度,这些化合物被评估为潜在的严重急性呼吸综合征冠状病毒2 3CL蛋白酶抑制剂。第一个测试的环糊精,即高度硫酸化的-β-环糊精,在 25 mM 磷酸盐缓冲液中浓度为 6% (m/v),使用动态涂有聚环氧乙烷的毛细管,施加电压为 15 kV,温度为25°C,被发现可以成功分离五种衍生物。检测和定量限与方法的绿色度分数一起计算,以评估该方法的分析和环境性能。此外,值得注意的是,使用两个不同的柱(直链淀粉三(3,5-二甲基苯基氨基甲酸酯)涂层和纤维素三(3,5-二氯苯基氨基甲酸酯)涂层)同时高效液相色谱分离相同化合物的对映体。对其固定在二氧化硅固定相上进行了研究。前者固定相和后者均无法在由正庚烷/2-丙醇80/20 (v/v)组成的流动相中分离所有衍生物。
更新日期:2024-01-16
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