Tandem Liquid chromatography–mass spectrometry

亚琛新的临床药理研究所的研究重点在于更好地了解人们对药物和外源物质反应的个体差异。由此产生的发现应该有助于为患者开发更安全、更有效和个性化的治疗方法。除了分析代谢异源物质的酶的遗传变异外，通过在血浆或其他生物样本中进行药物分析量化的个人代谢概况还允许个性化药物治疗。在人类的生物样本中，个体的代谢特征可以通过器官或细胞来检测。可以绘制代谢物和药物浓度与期望或不期望的药物效果之间的关联分析。质谱仪将用于临床研究项目中的药物定量和监测，以及作为临床药理学研究的一部分的细胞生物学或毒理学研究项目。具体地说，该设备将用于以下分析和研究领域：在不同组织培养中的个体药物代谢和酶动力学的调查，临床药物遗传学研究，离子通道的生物物理药理学，在临床毒理学研究的背景下阐明多氯联苯的人体代谢。当我们处理新陈代谢中罕见的副作用和特殊性时，有毒代谢物的测定可能与调查和鉴定新的生物转化产物一样必要。对细胞培养和组织样本的研究也针对这些问题，这就是为什么，特别是在个性化药物研究领域，有必要在非常低的浓度范围内测定药物，精确到皮摩尔范围--为此需要使用高分辨率质谱学方法。到目前为止，这些检查都是在申请人以前的工作中进行的，但在她新被任命到亚琛大学医院建立临床药理学的过程中，这里认为有必要使用这样的设备-也是为了支持大学医院的临床药理学研究。串联质谱仪将分散使用，位于职业医学研究所的设备池中，并提供必要的技术和科学质谱学专业知识和专家设备支持。该装置将用于药代动力学和毒代动力学领域的科学研究，这些方法将被纳入科学合作和合作研究项目(合作模式)。除了技术人员外，拥有足够MS经验的科学家和博士生也应该能够接触到该设备。该设备旨在在亚琛大学医院建立这种特定的方法，并使科学合作成为可能。

The research focus of the new institute of clinical pharmacology in Aachen lays in the better understanding of individual differences in people's reactions to drugs and xenobiotics. The resulting findings should serve to develop safer, more efficient and individually tailored therapies for patients. In addition to the analysis of genetic variations of enzymes that metabolize xenobiotic substances, individual metabolic profiling by drug analytic quantification in plasma or other biosamples allows to individualize drug therapies. In human bio-samples, individual metabolic profiles can be examined organ- or cell-specific. Associations analyses between concentrations of metabolites and drugs and the desired or undesirable drug effects can be drawn.The mass spectrometer will serve for drug quantification and monitoring in clinical research projects and in cell biology or toxicological research projects as part of clinical pharmacological research. Specifically, the device is to be used for the following analyzes and research areas: Investigations of the individual drug metabolism and enzyme kinetics in different tissue cultures, clinical pharmacogenetic research, biophysical pharmacology of ion channels, elucidation of the human metabolism of polychlorinated biphenyls in the context of clinical toxicological studies. As we deal with rare side effects and peculiarities in metabolism, determinations of toxic metabolites may be just as necessary as the investigation and identification of new biotransformation products formed. The investigations in cell cultures and tissue samples are also aimed at these questions, which is why, especially in the field of research on personalized medicine, the determination of drugs in very low concentration ranges is necessary, right down to the picomole range - for which the use of high-resolution mass spectrometric methods is required . So far, these examinations have been carried out at the applicant's previous job, but in the course of her new appointment to the University Hospital Aachen for the establishment of a clinical pharmacology, the need for such a device was considered necessary here - also to support clinical pharmacological research in the university hospital.The tandem mass spectrometer is to be used decentrally and located in the equipment pool of the Institute for Occupational Medicine with the necessary technical and scientific mass spectrometric expertise and expert equipment support. The device is to be used for scientific research in the field of pharmacokinetics and toxicokinetics and these methods are to be incorporated into scientific collaborations and collaborative research projects (cooperation model). In addition to the technical staff, access to the device should also be made possible for scientists and doctoral candidates with sufficient MS experience.The device is intended to establish this specific methodology at the University Hospital Aachen and to enable scientific collaborations.