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原位生长金属有机骨架协同体系用于开管毛细管电色谱对三种药物的对映体分离。

In-situ grown metal organic framework synergistic system for the enantioseparation of three drugs in open tubular capillary electrochromatography.

机构信息

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, P. R. China.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.

出版信息

J Sep Sci. 2022 Jul;45(14):2708-2716. doi: 10.1002/jssc.202100987. Epub 2022 Jun 9.

Abstract

Metal organic frameworks have received great attention as the chiral stationary phase for racemic drug separation because of their fascinating structures and properties. However, the most homochiral metal organic frameworks were constructed by rare and precious chiral organic ligands. In this work, an achiral metal organic framework, together with a natural chiral selector carboxymethyl β-cyclodextrin built a synergistic separation system in the open tubular capillary electrochromatography. The novel coated columns were developed by inducing metal organic framework nanoparticles to grow on the imidazolyl functional capillary inner wall. The baseline separations of hydroxychloroquine, ofloxacin, and atenolol were achieved in the synergistic separation system. The effects of the concentration of chiral selector, pH, voltage, and the concentration of organic additives were studied. Compared with chiral selector auxiliary bare capillary, the resolutions of three drugs were remarkably improved. The relative standard deviations for the retention time of intraday (n = 6), interday (n = 6), and column-to-column were less than 2.1, 2.6, and 5.2%, respectively. These results demonstrate that affordable synergistic separation systems are prospective for racemic drug enantioseparation in capillary electrochromatography.

摘要

金属有机骨架因其迷人的结构和特性而被广泛用作对映体药物拆分的手性固定相。然而,大多数同手性金属有机骨架是由稀有而珍贵的手性有机配体制成的。在这项工作中,一种非手性金属有机骨架与天然手性选择剂羧甲基-β-环糊精在开放管毛细管电色谱中构建了协同分离体系。通过诱导金属有机框架纳米粒子在咪唑基官能化毛细管内壁上生长,开发了新型涂覆柱。在协同分离体系中实现了羟氯喹、氧氟沙星和阿替洛尔的基线分离。研究了手性选择剂浓度、pH 值、电压和有机溶剂添加剂浓度的影响。与手性选择剂辅助的裸毛细管相比,三种药物的分辨率显著提高。日内(n=6)、日间(n=6)和柱间的保留时间的相对标准偏差分别小于 2.1%、2.6%和 5.2%。这些结果表明,在毛细管电色谱中,价格合理的协同分离系统有望用于对映体药物的拆分。

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