微量药物杂质和药物代谢物结构鉴定在新药研发整个过程中是经常遇到又极其费时费力的工作。在新药开发的早期，常首选液质联用技术进行这项研究。然而，针对药物分子的电喷雾串联质谱裂解机理研究既不深入，也欠系统，更缺乏一些可应用于结构鉴定中的普适性强的规律等关键问题；又鉴于大多数药物分子中含有杂原子，而这些杂原子通常为电喷雾质谱中的质子化活性位点，具有特殊的质谱裂解规律；为此，在前期科研工作基础上，本项目拟选择药物中具有代表性的含杂原子分子作为模型化合物，进行电喷雾串联质谱实验，通过质子化位点和取代基效应的研究，并辅以同位素标记实验和理论计算，总结推导并获得系列质谱裂解规律；以此为基础，选择分子结构中含杂原子的药物包括正在研发的创新候选药物为研究对象，建立应用ESI-MS在线、快速、专属和灵敏地鉴定微量或超微量复杂药物杂质和代谢物分子结构的新方法和新技术；为ESI-MS理论的丰富和完善提供科学的依据。

The structure identification of trace drug impurities and drug metabolite is often encountered in the entire process of drug discovery and extremely time-consuming and laborious work. LC/MS was used preferably to carry out this study in the early stage of new drugs R&D. Not only the mechanism of the fragmentation of drug-related molecules is not well understood but also it is lack of universal rules in ESI-MS/MS, therefore it is difficulty to identify drug structure. Since the majority of drug molecules contains heteroatoms which usually are the protonation sites in ESI-MS, on the basis of the results of our preliminary work, the common and representative of various drug molecules containing heteroatoms will be used as model compounds to conduct structural elucidation via ESI-MS/MS. In combination with isotope labeling experiments and theoretical calculations, investigation of the protonation sites and substituent effects, then mass spectral fragmentation patterns of model molecules are summarized. On this basis, the fast, specific and sensitive ESI-MS methods are established to identify the structure of trace drug impurities and drug metabolite, for the drugs or innovative drug candidates containing heteroatoms.