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新型可调重力介导毛细管电泳与磺酸丙基醚-β-CD 聚合物联合增强手性药物分离。

Enhancement of chiral drugs separation by a novel adjustable gravity mediated capillary electrophoresis combined with sulfonic propyl ether β-CD polymer.

机构信息

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

出版信息

Anal Chim Acta. 2023 Oct 23;1279:341781. doi: 10.1016/j.aca.2023.341781. Epub 2023 Sep 6.

DOI:10.1016/j.aca.2023.341781
PMID:37827633
Abstract

A water-soluble negative sulfonic propyl ether β-CD polymer (SPE-β-CDP) to be used as chiral selector in capillary electrophoresis (CE) was polymerized. The sulfonic substitution degree of each β-CD in SPE-β-CDP was statistically homogenized. The only one negative peak in electrophoretogram with indirect ultraviolate method proved its uniformity of electrophoretic behavior. There were 7.12 sulfonic substitution in β-CD unit and 164 μmole β-CD units in each gram of SPE-β-CDP, which corresponded a molecular weight of 7000 or more. Compared with monomer, SPE-β-CDP was lower effect on electrical current of CE, indicating a high concentration of SPE-β-CDP could be added. Its separation ability was verified by 12 chiral drugs. SPE-β-CDP also showed advantages of good water solubility, easy preparation and recovery to reduce the overall cost. However, five of 12 chiral drugs were hardly to be fully separated which was normal for any kind of chiral selector. A newly adjustable gravity mediated capillary electrophoresis (AGM-CE) technology was proposed and combined with SPE-β-CDP to enhance the chiral separation efficiencies of propranolol, salbutamol, omeprazole, ofloxacin and phenoxybenzamine which were markedly improved to 3.02, 1.17, 7.63, 4.14, and 2.81, respectively. Furthermore, its gradient mode (AGMg-CE) was also used to improve resolution through utilizing the zero mobility point, at which the effective apparent mobility of one racemate was zero. Resolutions of five chiral drugs were significantly improved, especially resolution of carvedilol changed from 0.43 to 1.0. These indicated SPE-β-CDP as chiral selector, AGM-CE and AGMg-CE as new CE technologies had a great potential in chiral separation.

摘要

一种水溶性负磺酸丙基醚-β-CD 聚合物(SPE-β-CDP)被用作毛细管电泳(CE)中的手性选择剂。SPE-β-CDP 中每个 β-CD 的磺酸取代度均具有统计均匀性。间接紫外法得到的电泳图谱中只有一个负峰,证明其电泳行为具有均一性。每个克 SPE-β-CDP 中β-CD 单元有 7.12 个磺酸取代基和 164μmoleβ-CD 单元,对应分子量在 7000 以上。与单体相比,SPE-β-CDP 对 CE 的电流影响较小,表明可以添加更高浓度的 SPE-β-CDP。通过 12 种手性药物验证了其分离能力。SPE-β-CDP 还具有水溶性好、易于制备和回收的优点,可以降低整体成本。然而,12 种手性药物中有 5 种很难完全分离,这在任何一种手性选择剂中都是正常的。提出了一种新的可调重力介导毛细管电泳(AGM-CE)技术,并与 SPE-β-CDP 结合,提高了普萘洛尔、沙丁胺醇、奥美拉唑、氧氟沙星和苯氧苄胺的手性分离效率,分别提高到 3.02、1.17、7.63、4.14 和 2.81。此外,还使用其梯度模式(AGMg-CE)通过利用零迁移点来提高分辨率,在该点,一种对映体的有效表观迁移率为零。五种手性药物的分辨率均有显著提高,尤其是卡维地洛的分辨率从 0.43 提高到 1.0。这些表明 SPE-β-CDP 作为手性选择剂,AGM-CE 和 AGMg-CE 作为新的 CE 技术在手性分离方面具有很大的潜力。

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