分子印迹及相关技术用于手性药物那格列奈的拆分-分析化学专业论文.docx

i i 摘 要 分子印迹技术是一项集高分子聚合物制备 高选择性分子识别 分离富集等 手段为一体的综合性技术 本论文应用分子印迹技术 以非磺脲类降血糖手性药 物那格列奈为模板分子 分别采用本体聚合法 原位聚合法 沉淀聚合法制备了 无定形 连续整体和微球形具有特定识别和手性拆分性能的分子印迹聚合物 用 作高效液相色谱手性固定相实现了那格列奈分子与其对映体的手性拆分 全文分 为如下五个部分 第一章 介绍了分子印迹技术的原理 研究应用和进展状况 并概述了高效 液相色谱及相关技术在药物分析中的应用 第二章 采用本体聚合法 原位聚合法 沉淀聚合法制备了不同形态那格列 奈分子印迹聚合物 并用作高效液相色谱手性固定相考察其对那格列奈分子与其 对映体的拆分色谱行为 第三章 考察了那格列奈印迹聚合物的吸附特性和手性分离过程中的热力学 性质 第四章 应用那格列奈分子印迹聚合物对那格列奈与其几何异构体进行拆分 并讨论了 MIP 分子识别机理 同时对分子印迹技术在结构类似物分离方面的应用 作了简单介绍 第五章 应用 HPLC ELSD 技术对药物中的胆酸 植物中的水苏糖进行了检测 并预测了这项技术与分子印迹技术相结合在药物分析中的应用前景 实验通过对那格列奈印迹聚合物合成 手性拆分的色谱行为 吸附特性和热 力学性质等内容的考察 验证了那格列奈印迹聚合物作为色谱手性固定相的可行 性和应用优势 关键词 分子印迹聚合物 高效液相色谱 手性固定相 那格列奈 ii ii Abstract Molecular Imprinting Technology (MIT) has been proved to be an effective tool for chiral separation, solid-phase extraction, sensors, etc. In this thesis, molecularly imprinted polymers (MIP) based on nateglinide, an orally drug of active secretagogue, were prepared and have been used as HPLC chiral stationary phases (CSP). The chromatographic performance, absorption and thermodynamic characteristics of chiral separation on MIP-CSP were investigated. There are five chapters in this thesis. In Chapter, the principle of MIT, polymerization methods, application of this technique and its future developments were introduced. And the applications of HPLC on chiral separation and HPLC-ELSD technology were also described. In Chapter, bulk, rod and microsphere MIP were prepared by different approaches. Experiments showed that all of those MIP had wonderful enantio-selectivities on nateglinide and its L-enantiomer even their chromatographic performances were different. In Chapter , the characteristics of adsorption and thermodynamics of nateglinide- MIP were investigated. The adsorption isotherms of neteglinide and L-enantiomer were studied by static method. Schatchard analysis indicated that two classes of binding site were present in the imprinted polymers. In Chapter , separation of neteglinide and its cis-isomer on