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手性β受体阻滞剂的对映体分离用聚去甲肾上腺素包覆的纳米粒子和手性毛细管电泳法。

Enantioseparation of chiral β-blockers using polynorepinephrine-coated nanoparticles and chiral capillary electrophoresis.

机构信息

Ministry of Education Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, Guangdong, China.

出版信息

Anal Bioanal Chem. 2019 Apr;411(10):2121-2129. doi: 10.1007/s00216-019-01641-4. Epub 2019 Feb 8.

Abstract

A method of combining magnetic solid-phase separation (MSPE) and chiral capillary electrophoresis (CE) is developed for enantioseparation of trace amounts of β-blockers. Polynorepinephrine-functionalized magnetic nanoparticles (polyNE-MNPs) are synthesized and applied to simultaneously extract three β-blockers (carteolol, metoprolol, and betaxolol). The prepared polyNE-MNPs are spherical with a diameter of 198 ± 17 nm and the thickness of the polyNE coating is about 14 nm. PolyNE possesses abundant catechol hydroxyl and secondary amine groups, endowing the MNPs with excellent hydrophilicity. Under the optimum conditions, the extraction efficiencies of polyNE-MNPs for β-blockers are in the range of 89.6 to 100%, with relative standard deviations (RSDs) below 3.5%. The extraction process can be finished in 4 min. Field-enhanced sample injection (FESI) in chiral CE is constructed to further enhance the sensitivities of β-blocker enantiomers. The limits of detection for β-blocker enantiomers by the FESI-CE with polyNE-MNPs are in the range of 0.401 to 1.59 ng mL. The practicability of this method in real samples is evaluated by analysis of human urine samples. The recoveries for each enantiomer of β-blockers in the real samples range from 89.5 to 92.8%, with RSDs ranging from 0.37 to 5.9%. The whole detection process can be finished in less than 0.5 h. The method demonstrates its great potential in the pharmacokinetic and pharmacodynamic studies of chiral drugs in humans. Graphical abstract ᅟ.

摘要

一种结合磁固相萃取(MSPE)和手性毛细管电泳(CE)的方法被开发用于痕量β受体阻滞剂对映体的分离。合成了多去甲肾上腺素功能化磁性纳米粒子(polyNE-MNPs),并将其用于同时提取三种β受体阻滞剂(卡替洛尔、美托洛尔和倍他洛尔)。制备的 polyNE-MNPs 呈球形,直径为 198 ± 17nm,polyNE 涂层的厚度约为 14nm。polyNE 具有丰富的儿茶酚羟基和仲胺基团,使 MNPs 具有优异的亲水性。在最佳条件下,polyNE-MNPs 对β受体阻滞剂的萃取效率在 89.6%至 100%之间,相对标准偏差(RSD)低于 3.5%。萃取过程可以在 4 分钟内完成。在手性 CE 中构建场增强样品进样(FESI)以进一步提高β受体阻滞剂对映体的灵敏度。用 polyNE-MNPs 的 FESI-CE 检测β受体阻滞剂对映体的检出限在 0.401 至 1.59ng mL 范围内。通过分析人尿样评估了该方法在实际样品中的实用性。实际样品中每个β受体阻滞剂对映体的回收率在 89.5%至 92.8%之间,RSD 范围在 0.37%至 5.9%之间。整个检测过程可以在不到 0.5 小时内完成。该方法在人体手性药物的药代动力学和药效学研究中具有很大的应用潜力。

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