Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), China Pharmaceutical University, No.24 Tongjiaxiang, Nanjing, Jiangsu, 210009, People's Republic of China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjiaxiang, Nanjing, Jiangsu, 210009, People's Republic of China.
Mikrochim Acta. 2020 Feb 19;187(3):178. doi: 10.1007/s00604-020-4144-8.
Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were prepared, and used as a support to attach gold nanoparticles (AuNP) via Au-S bond. Pepsin, acting as a chiral selector, was linked to the surface of the carboxyl-modified AuNP through a hydrochloride/N-hydroxysuccinimide coupling reaction. The material was characterized by scanning electron microscopy, energy dispersive X-ray spectrometry, transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and N adsorption-desorption isotherm. The pepsin@AuNP@poly(GMA-co-EDMA) monolith showed preferable enantioselectivity for hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), labetalol (LAB), nefopam (NEF), clenbuterol (CLE), amlodipine (AML) and chlorpheniramine (CHL) in capillary electrochromatography (CEC). These racemic drugs were monitored at the maximum absorption wavelength (220 nm for HXQ, CHQ, HXY, LAB, NEF; 240 nm for AML; 215 nm for CLE, CHL). In comparison with the pepsin@poly(GMA-co-EDMA) monolith loaded with 5 nm AuNP, the pepsin@poly(GMA-co-EDMA) monolith loaded with 13 nm AuNP shows significantly enhanced enantiomeric resolution (HCQ: 0.62 → 3.45; CHQ: 0.60 → 2.11; HXY: 0.49 → 2.30; LAB: 1.03 → 2.45, 1.45 → 3.46, 0 → 0.67; NEF: 0.53 → 1.29; CLE: 0.42 → 0.56; AML: 0 → 0.83; CHL: 0.24 → 0.55). Pepsin concentration, buffer pH value, buffer concentration and applied voltage were investigated in detail with (±) HCQ and (±) HXY as model analytes. The reproducibility of intra-day, inter-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic presentation of the preparation of gold nanoparticles (AuNP) modified.
聚（甲基丙烯酸缩水甘油酯）-共-（乙二醇二甲基丙烯酸酯）[聚（GMA-co-EDMA）]整体柱的制备，并用作通过 Au-S 键将金纳米粒子（AuNP）附着的载体。胃蛋白酶作为手性选择剂，通过盐酸盐/N-羟基琥珀酰亚胺偶联反应连接到羧基改性的 AuNP 的表面。该材料通过扫描电子显微镜、能量色散 X 射线光谱、透射电子显微镜、热重分析、傅里叶变换红外光谱和 N 吸附-解吸等温线进行了表征。胃蛋白酶@AuNP@聚（GMA-co-EDMA）整体柱在毛细管电色谱（CEC）中对羟氯喹（HCQ）、氯喹（CHQ）、羟嗪（HXY）、拉贝洛尔（LAB）、奈福泮（NEF）、克仑特罗（CLE）、氨氯地平（AML）和氯苯那敏（CHL）表现出较好的对映选择性。这些外消旋药物在最大吸收波长（220nm 用于 HXQ、CHQ、HXY、LAB、NEF；240nm 用于 AML；215nm 用于 CLE、CHL）下进行监测。与负载 5nm AuNP 的胃蛋白酶@聚（GMA-co-EDMA）整体柱相比，负载 13nm AuNP 的胃蛋白酶@聚（GMA-co-EDMA）整体柱显示出显著增强的对映体分辨率（HCQ：0.62→3.45；CHQ：0.60→2.11；HXY：0.49→2.30；LAB：1.03→2.45、1.45→3.46、0→0.67；NEF：0.53→1.29；CLE：0.42→0.56；AML：0→0.83；CHL：0.24→0.55）。详细研究了（±）HCQ 和（±）HXY 作为模型分析物时，胃蛋白酶浓度、缓冲液 pH 值、缓冲液浓度和施加电压。还探讨了日内、日间和柱间重现性，结果令人满意。
