功能化磁性纳米介质萃取新技术及其在痕量大环内酯类抗生素检测中的应用研究

The project is aimmed to develop functionalized magnetic nanoparticles-based extration technologies and its application for extraction and determination of trace macrolide antibiotics (MALs) in food.The basic strategis are as follows. Novel core-shell magnetic nanoparticles will be fabricated by introducing funcationalized coating onto magnetic nanoparticles as core. Highly selective coatings including funcationalized silica coating and surface molecular imprinting polymer (SMIP) coating will be developed onto magnetic nanoparticles for selective extraction of target MALs from very complex matrix. For functionalized silica coating, restricted access material (RAM) with chemically-bonded C18 groups inside the inner pores and the chemical bonding methodologies will be investigated for introducing mixed funcational groups (e.g. C18 and cation exchange groups) in consideration of weak base and hydrophobic property of MALs compounds, aimming to enhance extraction ability and improve the dispersity of nanoparticles. For SMIP coating, take erythrocin, azithromycin and medemycin as module molecule, the corresponding SMIP coating onto magnetic nanoparticles will be respectively fabricated for selective extraction of common used MALs. By combination of above extraction technologies and high performance liquid chromatography, it is aimmed to devlope fast extraction and determination technology of trace MALs.

旨在发展复杂样品中痕量大环内酯类抗生素（Macrolide antibiotics,MALs）检测的功能化磁性纳米介质萃取新技术及其分析方法。基本策略为：构建以磁性纳米颗粒为内核、表面功能化涂层为壳的新型核壳型磁性纳米介质；拟发展功能化硅胶涂层和表面分子印迹聚合物(Surface molecular imprinting polymer,SMIP)涂层实现对复杂基体中目标物的高选择性萃取。功能化硅胶涂层：根据MALs分子弱碱型脂溶性强的特点，拟通过发展限制进入型内孔表面键合C18或发展硅胶涂层的表面键合方法，引入极性C18混合官能团（比如阳离子交换基团-C18）以增强萃取效果和改善纳米介质的分散性；SMIP涂层：分别以红霉素、阿奇霉素和麦迪霉素为模板分子在磁性纳米颗粒表面构建相应的SMIP涂层实现对常见MALs高选择性萃取。通过上述萃取技术、结合高效液相色谱发展痕量MALs快速检测技术。

发展出系列新型大环内酯选择性吸附剂，包括磁性限进材料、分子印迹聚合物、磁性纳米分子印迹、磁性表面分子印迹、磁性C18-SO42-双功能团、磁性石墨烯等。这些吸附剂对大环内酯分子表现出良好的富集效果（富集因子为200-800倍）、有效的特异性识别及对基质效应的抗干扰能力。磁性吸附剂的引入在处理大体积样品以及相分离方面表现出远优于常规吸附剂的特性；结合液相色谱分离系统，上述吸附剂将为分析环境、食品等领域中样品中痕量大环内酯提供可靠的技术手段；基于聚乙烯醇表面共聚技术发展出系列新型强极性色谱分离介质或吸附剂，该方法具有绿色（不涉及到有机溶剂的使用）、快速（制备时间约4小时），普适性（掺杂合适的聚合物理论上可引入任何所需要的官能团）。该方法可适用于现有所有商品化类型的微球，为快速制备强极性固定相提供了一种新思路；利用自行发展的表面正电荷修饰反相C18混合官能团色谱介质成功实现了对9种大环内酯的基线分离，克服了常规反相C18色谱柱分离大环内酯普遍存在的色谱峰拖尾、柱效低等问题。这为有效分离其它类型大环内酯及其它弱碱性药物提供了一种新途径。