基于毛细管电泳/电色谱-质谱联用技术的药物分析新方法

Capillary electrophoresis/electrochromatography-mass spectrometry (CE/CEC-MS) is a hyphenated technique, which develops on the basis of liquid chromatography–mass spectrometry. It integrates advantages of high performance and selectivity in CE/CEC and high sensitivity and strong structure elucidation in MS. There are some scientific bottleneck problems for the development of CE/CEC-MS. There are few commercially available CEC columns, which have specific selectivity and are able to couple with MS detection. Some analytes have poor solubility, separation selectivity in aqueous solution in CE/CEC separation and low electrospray efficiency in MS detection. To solve these problems, novel polymeric monolithic columns using ionic liquids and styrenes as functional monomers and open tubular columns modified with novel covalent organic frameworks and metal organic frameworks as stationary phases will be developed. Key technology for the modulation of electroosmotic flow, separation selectivity in CEC separation and hyphenation with MS detection will be developed. Another part of work will be focused on the development of CE-MS methods for analysis of active components in traditional Chinese medicines such as Osmanthus fragrans fruits. The key technology for improvement of separation selectivity in CE-MS and detection sensitivity in MS will be developed. The development of CE/CEC-MS methodology will make great contribution to the development of pharmaceutical analysis and is significantly important for scientific research and application.

毛细管电泳/电色谱-质谱(CE/CEC-MS)联用技术是在LC-MS基础上发展起来的药物分析新技术,结合了电泳、电色谱的高效、高分离选择性，质谱的高灵敏度及强结构解析等优点。目前存在主要瓶颈问题为：缺乏具有特征分离选择性并能与质谱检测相兼容的电色谱柱；有些药物在水相中溶解度小、稳定性及分离选择性差，电喷雾离子化效益低导致质谱检测灵敏度不高等。针对这些问题，拟研制以离子液体与苯乙烯类功能单体共聚合的整体柱、以金属有机骨架及共价有机骨架等新型分子识别材料为固定相的开管柱，解决电渗流、分离选择性调控，CEC分离与质谱检测兼容性等关键技术问题；拟以中药桂果等为对象，研究活性组分的CE-MS分析新方法，解决中药活性组分的分离选择性调控、提升离子化效益即质谱检测灵敏度的关键技术问题，建立新型CE/CEC-MS联用新方法。该项目对药物分析新方法研究具有极其重要的科学研究和应用价值。

按照任务书要求认真组织实施，圆满完成了计划书中的各项任务。本课题旨在开展基于毛细管电泳/电色谱-质谱联用技术的药物分析新方法研究，针对目前具有特征分离选择性并能与质谱检测相兼容电色谱柱缺乏有些药物在水相中溶解度小、稳定性及分离选择性差，电喷雾离子化效益低导致质谱检测灵敏度低、CEC分离与MS检测兼容性差等科学问题，研制成功一系列以手性识别材料、离子液体与苯乙烯类等功能单体共聚合的整体柱、以金属有机骨架及共价有机骨架等新型分子识别材料为固定相的开管柱，并应用于中药活性组分和手性药物分析，建立了一系列新型CE/NACE/CEC-MS联用新方法。主要内容包括:（1）新型毛细管电泳/电色谱-质谱联用技术及其在药物分析中应用，（2）手性药物毛细管电色谱柱技术及其应用研究，（3）具有特征分离选择性、高性能新型毛细管电色谱柱技术和固相微萃取新装置与技术，（4）新型固相微萃取技术及其在药物分析中应用，（5）基于毛细管电动分离技术的抑制剂筛选新方法。. 该项目实施期间共发表标注基金号的SCI论文51篇，获批国家发明授权专利11项，作为会议执行共同主席组织承办了第4届国际药物分析前沿研究进展研讨会（eAPA2022）。在国内外国际、国内学术会议中应邀做大会报告、主旨报告及邀请报告25余次，培养博士生7名、硕士生12名。