基于敞开式质谱检测的药物液相色谱高通量筛选研究

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。.本研究拟将敞开式质谱作为高通量多孔板微反应底物和产物的快速、无标记检测方法，结合液相色谱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。核心研究内容包括：多孔板生化微反应敞开式（解吸附电喷雾离子化、解吸附电晕束离子化）质谱快速检测研究、高通量分离、结构鉴定及活性表征一体化系统构建及系统的实用性考察。

Lead compound screening is the key procedure for the drug discovery. In the high-throughput (HTS) and ultra-high throughput screening (UHTS) process, the development of accurate, rapid, miniaturized 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 project, we will use ambient MS as an universal and label-free detection tool for the HTS of array-plate. 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. As a core of the study, different ambient ionization sources, i.e. DESI, DART, and DCBI, will be investigated for the monitor of biochemical reactions. The purpose of the project is to develop a HTS for drug lead compounds from the natural products and traditional Chinese medicine.