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双(2-羟丙基)-β-环糊精和 5,10,15,20-四(4-羟基苯基)卟啉体系作为一种新型的手性-非手性选择剂复合物,用于毛细管电泳中具有抗癌活性的氨基酸醇衍生物的对映体分离。

Dual 2-Hydroxypropyl-β-Cyclodextrin and 5,10,15,20-Tetrakis (4-Hydroxyphenyl) Porphyrin System as a Novel Chiral-Achiral Selector Complex for Enantioseparation of Aminoalkanol Derivatives with Anticancer Activity in Capillary Electrophoresis.

机构信息

Chair and Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.

Chair and Department of Biochemistry, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.

出版信息

Molecules. 2021 Feb 13;26(4):993. doi: 10.3390/molecules26040993.

Abstract

In this study, a complex consisting of 2-hydroxypropyl-β-cyclodextrin and 5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin, (named dual chiral-achiral selector complex) was used for the determination of two novel potential anticancer agents of (I) and (II) aminoalkanol derivatives. This work aimed at developing an effective method that can be utilized for the determination of I (S), I (R), and II (S) and II (R) enantiomers of (I) and (II) compounds through the use of a dual chiral-achiral selector complex consisting of hydroxypropyl-β-cyclodextrin and 5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin system by applying capillary electrophoresis. This combination proved to be beneficial in achieving high separation selectivity due to the combined effects of different modes of chiral discrimination. The enantiomers of (I) and (II) compounds were separated within a very short time of 3.6-7.2 min, in pH 2.5 phosphate buffer containing 2-hydroxypropyl-β-cyclodextrin and 5,10,15,20-tetrakis (4-hydroxyphenyl) porphyrin system at a concentration of 5 and 10 mM, respectively, at 25 °C and +10 kV. The detection wavelength of the detector was set at 200 nm. The LOD for I (S), I (R), II (S), and II (R) was 65.2, 65.6, 65.1, and 65.7 ng/mL, respectively. LOQ for I (S), I (R), II (S), and II (R) was 216.5, 217.8, 217.1, and 218.1 ng/mL, respectively. Recovery was 94.9-99.9%. The repeatability and reproducibility of the method based on the values of the migration time, and the area under the peak was 0.3-2.9% RSD. The stability of the method was determined at 0.1-4.9% RSD. The developed method was used in the pilot studies for determining the enantiomers I (S), I (R), II (S), and II (R) in the blood serum.

摘要

在这项研究中,使用了由 2-羟丙基-β-环糊精和 5,10,15,20-四(4-羟基苯基)卟啉组成的复合物(命名为双手性-无手性选择器复合物),用于测定两种新型潜在抗癌药物(I)和(II)氨基烷醇衍生物。本工作旨在开发一种有效的方法,通过使用由 2-羟丙基-β-环糊精和 5,10,15,20-四(4-羟基苯基)卟啉组成的双手性-无手性选择器复合物,通过应用毛细管电泳法来测定(I)和(II)化合物的 I(S)、I(R)、II(S)和 II(R)对映异构体。这种组合由于不同手性识别模式的综合作用,有利于实现高分离选择性。(I)和(II)化合物的对映异构体在非常短的时间内(3.6-7.2 分钟)分离,在 pH 2.5 磷酸盐缓冲液中,2-羟丙基-β-环糊精和 5,10,15,20-四(4-羟基苯基)卟啉系统的浓度分别为 5 和 10 mM,在 25°C 和+10 kV 下。检测器的检测波长设置为 200nm。I(S)、I(R)、II(S)和 II(R)的检出限分别为 65.2、65.6、65.1 和 65.7 ng/mL。I(S)、I(R)、II(S)和 II(R)的定量限分别为 216.5、217.8、217.1 和 218.1 ng/mL。回收率为 94.9-99.9%。该方法的重复性和重现性基于迁移时间和峰面积的值为 0.3-2.9%RSD。方法的稳定性在 0.1-4.9%RSD 下确定。所建立的方法用于初步研究测定血清中 I(S)、I(R)、II(S)和 II(R)的对映异构体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6221/7918572/5ef7cc125daa/molecules-26-00993-g001.jpg

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