Triple quadrupole linear ion trap mass spectrometer coupled to a HPLC system

提出的三重四极线型离子陷阱质谱仪与高压液相色谱系统联用，代表了一种用于分析有机小分子(<lt；2000 Da)的高特异性和高灵敏度的装置系统。该装置一方面应能够量化药物及其代谢物的最低浓度，以及复杂生物基质(如血清、器官匀浆、细胞裂解物)中的内源性物质(生物标记物)。另一方面，该设备系统应用于体外系统(如细胞系、微生物体、有机体)以及人和动物组织样本中的蛋白质，如药物转运体和代谢酶的鉴定和定量，使用所谓的靶向蛋白质组学方法。此外，还可以进行以前只能用两种不同类型的质谱仪(即离子陷阱质谱仪和三重四极质谱计)进行的联合实验。应用工作组的总体研究目标是表征与药物治疗的药代动力学、疗效和安全性密切相关的代谢酶和转运蛋白的表达、调节和功能。所申请的仪器系统及其关联的最高测量灵敏度和特异度的组合是实现研究目标设定的必要前提。罗斯托克大学医学中心的药理学和毒理学研究所已经在LC-MS/MS分析领域拥有丰富的经验，并拥有适当的设备。然而，现有的旧设备一方面大量使用，另一方面不够灵敏或在技术上不适合解决当前的问题。所要求的设备将使我们能够以以前无法想象的灵敏度和特异性进行我们自己的研究分析。除了实现您自己的研究问题，该设备系统还用于大学内部以及国内和国际合作的框架内。这里的主要目标一方面是建立稳定和长期的研究合作，另一方面是以高排名出版物的形式进行可持续的科学开发，如果可能的话，还包括专利申请。

The proposed triple quadrupole linear ion trap mass spectrometer coupled to a high-pressure liquid chromatography system (HPLC-MS/MS) represents a device system for the highly specific and highly sensitive analysis of small organic molecules (< 2000 Da). The device should on the one hand enable quantification of lowest concentrations of drugs and their metabolites, as well as endogenous substances (biomarkers) in complex biological matrices (e.g. serum, organ homogenates, cell lysates). On the other hand, the device system should be used for the identification and quantification of proteins such as drug transporters and metabolizing enzymes in in vitro systems (e.g. cell lines, microsomes, organoids) and human and animal tissue samples using the so-called targeted proteomics approach.For the presented aims, the device applied for represents the optimal research platform, as it combines the highest specificity with the highest measurement sensitivity. In addition, combined experiments can be carried out that previously could only be carried out with two different types of mass spectrometers (i.e., ion trap mass spectrometer and triple quadrupole mass spectrometer). The overall research goal of the applying working group is the characterization of the expression, regulation and function of metabolizing enzymes and transport proteins, which are of great relevance for the pharmacokinetics, efficacy and safety of drug therapy. The device system applied for and the associated combination of the highest measurement sensitivity and specificity is an essential prerequisite for the realization of the research goals set. The Institute for Pharmacology and Toxicology at the Rostock University Medical Center already has extensive experience in the field of LC-MS/MS analysis and also has the appropriate equipment. However, the existing old devices are on the one hand heavily used and on the other hand not sufficiently sensitive or technically not suitable to be able to address the current issues. The requested device would enable us to carry out our own research analyzes with previously unimagined sensitivity and specificity.In addition to realizing your own research questions, the device system is also used within the framework of university-internal, as well as national and international cooperation. The main goal here is on the one hand the establishment of stable and long-term research cooperations and on the other hand a sustainable scientific exploitation in the form of high-ranking publications and, if possible, also patent applications.