Mass spectrometer (LC-MS)

该资助申请用于高灵敏度质谱仪，包括用于药物和内源性代谢物分析的高效液相色谱系统和相关软件。除了已知药物、内源性代谢物和肽的定量外，该系统还将支持迄今为止结构未知分子的定性鉴定。临床药理学和临床毒理学主席的质谱设施正在自己的研究项目以及合作中开发和应用各种各样的小内源性代谢物和药物在不同基质中的定量方法。所要求的系统应取代一台已停止使用的旧质谱仪，因此应产生新的分析能力。重点在于具有高分析灵敏度的液相色谱质谱仪系统，以实现检测和定量的低限，其远低于质谱设施中当前可用的质谱仪的检测和定量的低限。除了上述高灵敏度的定量，新的质谱仪将扩大目前的可能性，在非靶向代谢组学的背景下。最大的挑战之一在于正确识别检测到的信号。所要求的质谱仪可以分析具有额外碎片层的碎片模式，这构成了结构解析的重要辅助，因此可以帮助提高非靶向代谢组学分析的有效性。此外，计划使用市售试剂盒进行靶向代谢组学分析，并配备所要求的系统，以补充非靶向代谢组学分析。

This grant application is for a highly sensitive mass spectrometer including a high-performance liquid chromatography system and associated software for the analytics of drugs and endogenous metabolites. Besides the quantification of known drugs, endogenous metabolites and peptides, this system will also support the qualitative identification of structurally so far unknown molecules. The mass spectrometry facility at the Chair of Clinical Pharmacology and Clinical Toxicology is developing and applying quantitative methods for a wide variety of small endogenous metabolites and drugs in different matrices in own research projects as well as in co-operations. The requested system is supposed to replace an old mass spectrometer, that went out of service, and therefore new analytical capacities should be generated. The focus lies on a liquid chromatography mass spectrometer system with high analytical sensitivity in order to achieve low limits of detection and quantification, which are well below those of mass spectrometers currently available at the mass spectrometry facility. Besides the afore mentioned highly sensitive quantification, the new mass spectrometer will expand the present possibilities in the context of untargeted metabolomics. One of the biggest challenges lies in the correct identification of detected signals. The requested mass spectrometer can analyze fragmentation patterns with an additional layer of fragmentation, which constitutes as an important aid for structure elucidation, and hence can help to increase the validity of untargeted metabolomics analyses. Furthermore, it is planned to use commercially available kits for targeted metabolomics with the requested system to complement untargeted metabolomics analyses.