基于硼酸亲和糖基印迹与UPLC-MS/MS技术的糖肽类抗生素分离分析新方法研究

Glycopeptide antibiotics are supposed to the last defense line for antibacterial, and have become life-saving medicines for intractable drug resistant infections in critically ill patients. Metabolic monitoring of glycopeptide antibiotic medication is a prerequisite and requirement for the rational use of drugs; its detecting in environment and food samples provides theory and data foundation for epidemiological evaluation of specific populations for their exposure. In this project, we select a proper glycosyl group of glycopeptide antibiotics as the epitope to prepare surface imprinted SiO2 microspheres. Firstly, the surface of silica microspheres are modified by iniferters and boronic groups. And then the covalently self-assembly of boronic monomers and the template are optimized. Next, the imprinting materials are prepared through choosing biocompatibility/thermo-sensitive monomers and epitope imprinting technique. The resulting imprinted microspheres are used for group-selective extraction and enrichment of target glycopetide antibiotics from complex matrices. Subsequently, ultra-performance liquid chromatography-mass spectrometry is used for qualitative and quantitative analysis of the target antibiotics, establishing a highly sensitive and selective method for glycopeptide antibiotics detection. In brief, the implementation of this project aims to explore new ideas for selective separation and recognition of glycoproteins and other glycopetides, and provide a technique support for effective separation and accurate detection of glycopeptide antibiotics in complex matrix samples.

糖肽类抗生素被认为是抗菌药物的最后一道防线，成为顽固性耐药菌感染危重病人的救命药物。糖肽抗生素给药后的代谢监测是合理用药的前提与必要条件；环境和食品中糖肽抗生素的检测将为流行病学评价特定人群对其暴露程度提供理论和数据依据。本项目以糖肽类抗生素为研究对象，通过筛选糖肽类抗生素的糖基为模板分子，对二氧化硅微球表面进行引发剂、硼酸等功能化修饰；优化硼酸功能单体与模板分子的共价自组装，选择生物相容性、温敏性功能单体，运用抗原决定基法进行表面印迹，制备能同时高效分离富集多种糖肽类抗生素的分子印迹聚合物微球，用于选择性萃取复杂体系中的糖肽类抗生素。然后通过超高效液相色谱分离质谱解析对其进行定性定量分析，建立一种高选择性分离富集及高灵敏度检测糖肽类抗生素的方法。项目的实施为糖肽及糖蛋白的分离富集探索新的研究思路，为复杂基质样品中糖肽类抗生素的高效分离和准确测定提供技术支撑。

糖肽类抗生素被认为是抗菌药物的最后一道防线，成为顽固性耐药菌感染危重病人的救命药物。糖肽抗生素给药后的代谢监测是合理用药的前提与必要条件；环境和食品中糖肽抗生素的检测将为流行病学评价特定人群对其暴露程度提供理论和数据依据。本项目以糖肽类抗生素为研究对象，通过筛选糖肽类抗生素的糖基为模板分子，优化硼酸功能单体与模板分子的共价自组装，选择生物相容性、温敏性功能单体，进行分子印迹聚合反应，制备能同时高效分离富集多种糖肽类抗生素的分子印迹聚合物微球，用于选择性萃取复杂体系中的糖肽类抗生素。然后通过超高效液相色谱分离质谱解析对其进行定性定量分析，建立一种高选择性分离富集及高灵敏度检测糖肽类抗生素的方法。项目的实施为糖肽及糖蛋白的分离富集探索新的研究思路，为复杂基质样品中糖肽类抗生素的高效分离和准确测定提供技术支撑。