基于敞开式质谱检测的药物高压液相色谱高通量筛选研究

Study on high pressure liquid chromatography-high-throughput screening for drugs based on ambient mass spectrometry

中文关键词:  高压液相色谱  敞开式质谱  高通量筛选  天然产物

英文关键词:high pressure liquid chromatography  ambient mass spectrometry  high-throughput screening  natural product

中文摘要:

      药物筛选是整个药物发现过程的起点。在高通量和超高通量筛选中, 建立准确、快速、微型化和无标记的分析化学方法是其核心内容。敞开式(常温常压)质谱于2004年提出后, 因其可实现无需样品预处理的快速质谱分析而得到迅速发展; 相对于电喷雾电离质谱, 其基质效应小, 分析速度快, 已在不同形态样品快速分析、生物成像分析等领域发挥出重要作用。本研究将敞开式质谱作为高通量筛选的快速、无标记检测方法, 结合高压液相色谱法分离在线结构鉴定及电雾式检测, 获得分离化合物的分子量及绝对质量, 结合活性筛选结果获取分离化合物的活性量效关系及活性动力学行为, 从而建立针对天然产物复杂体系的新型高通量酶抑制剂筛选系统。

英文摘要:

      Lead compound screening is the key procedure for the drug discovery. In the high-throughput screening (HTS) and ultra-high throughput screening (UHTS) process, the development of accurate, rapid, mi-niaturized and label-free screening detection methods has been the core research field. After development of ambient mass spectrometry in 2004, the technique has been widely studied and applied because of its particular strongpoints such as low matrix effect, rapid analysis etc. It has been applied in different research fields such as bio-imaging, rapid analysis. In this paper, we will use ambient mass spectrometry as a universal and label-free detection tool for the HTS. Combining the ambient MS screening system with HPLC-multi-detection system, a HPLC high-throughput screening for drugs based on ambient mass spectrometry will be developed. The purpose of the paper is to develop a HTS for drug lead compounds from the natural products and traditional Chinese medicine.