Sun Xiaodong, Yu Tao, Xu Guangfu, Du Yingxiang, Chen Jiaquan, Li Xiaoqi
Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, Nanjing, 210009, P. R. China.
Chirality. 2019 Feb;31(2):118-126. doi: 10.1002/chir.23035. Epub 2019 Jan 4.
In this work, a new capillary electrokinetic chromatography (EKC) approach using ethanediamine-bonded poly (glycidyl methacrylate) (Ami-PGMA) microspheres as pseudostationary phases (PSPs) for enantioseparation with a polysaccharide, chondroitin sulfate E (CSE), as the chiral selector. The CSE@Ami-PGMA EKC system was applied to enantioseparate basic drugs, and distinct improved separations of tested enantiomers were obtained while comparing with the single CSE system (the resolution increased from 0.41 to 1.26 for nefopam, from 1.24 to 2.15 for laudanosine, and from 0.92 to 2.36 for amlodipine). The Ami-PGMA microspheres were fully characterized by scanning electron microscopy (SEM) and Fourier Transform Infrared (FT-IR) spectroscopy, and the results showed Ami-PGMA microspheres were uniform and spherical in size (1 μm). Several principal parameters were systematically investigated, and the optimal chiral separations were obtained with Tris/H PO (20 mM, pH 2.4, and 3.4 for NEF) containing 2.5% (w/v) CSE and 20-μg Ami-PGMA microspheres in 20°C. Subsequently, the concentrations of Ami-PGMA microspheres and CSE were proved to be the dominant factors for the separation in the CSE@Ami-PGMA EKC system by Statistical Product and Service Solutions (SPSS).
在本研究中,一种新的毛细管电动色谱(EKC)方法被开发出来,该方法使用乙二胺键合的聚甲基丙烯酸缩水甘油酯(Ami-PGMA)微球作为假固定相(PSP),以多糖硫酸软骨素E(CSE)作为手性选择剂进行对映体分离。CSE@Ami-PGMA EKC系统被应用于对碱性药物的对映体分离,与单一的CSE系统相比,测试对映体的分离效果有显著改善(奈福泮的分离度从0.41提高到1.26,劳丹诺辛从1.24提高到2.15,氨氯地平从0.92提高到2.36)。通过扫描电子显微镜(SEM)和傅里叶变换红外光谱(FT-IR)对Ami-PGMA微球进行了全面表征,结果表明Ami-PGMA微球尺寸均匀且呈球形(1μm)。系统研究了几个主要参数,在20℃下,含有2.5%(w/v)CSE和20μg Ami-PGMA微球的Tris/H₃PO₄(20mM,pH 2.4,NEF为pH 3.4)条件下获得了最佳手性分离效果。随后,通过统计产品与服务解决方案(SPSS)证明,在CSE@Ami-PGMA EKC系统中,Ami-PGMA微球和CSE的浓度是分离的主要因素。