High performance liquid chromatography electrospray tandem mass spectrometry for quantitative determination of biomarkers, drugs and metabolites in biological matrices

该提案包括购买QTRAP LC-MS/MS系统。该仪器是一种混合质谱仪，结合了许多传统的离子阱功能，但提供三重四极定量性能。这台仪器至关重要，因为我们在2011年6月淘汰了一台使用了19年的SCIEX API 3+仪器。因此，QTRAP LC-MS/MS的获得对于我们的研究计划的成功至关重要，该研究计划由NSERC发现资助支持，该资助名为：“使用差异和系统性蛋白质组探索策略发现疼痛传递的神经蛋白质组决定因素”，于2010年3月收到，为期5年。QTRAP LC-MS/MS仪器为蛋白质组学、肽组学和药物发现提供了无与伦比的定性性能，以及精确定量所需的宽动态范围，这对我们的研究活动至关重要。此外，所提出的仪器需要使用多重同量异位素标记技术和特定的多反应监测（MRM）到慢性和神经性疼痛的实验动物模型中来量化蛋白质表达。MRM技术是定量生物标志物发现和验证的金标准。蛋白质和肽定量方法的性能在生物标志物研究中很重要，因为它用于确定蛋白质表达，进行主成分分析（PCA）并定义用于诊断和预后目的的有效多参数谱。此外，这些类型的仪器是在复杂的生物基质中进行药物和代谢物定量的绝佳选择。药物药代动力学和代谢是动物药理学研究的关键要素，也是我们高素质的科学家在生物医学研究培训计划的一个组成部分。QTRAP LC-MS/MS的收购将大大有助于我们努力开发疼痛传递的新机制知识，识别特定的生物标志物，并为创新疼痛疗法的开发奠定基础。这种新的LC-MS/MS将对我们的研究活动和高素质人员（HQP）的培训产生直接影响。

This proposition includes the acquisition of a QTRAP LC-MS/MS System. This instrument is a hybrid mass spectrometer that combines many conventional ion trap functionalities but deliver triple quadrupole quantitative performance. This instrument is crucial since we retired an 19 years old SCIEX API 3+ instrument in June 2011. Thus, the acquisition of the QTRAP LC-MS/MS is critical for the success of our research program supported by an NSERC discovery grant entitled:"Discovery of neuroproteomic determinants of pain transmission using differential and systematic proteome exploration strategies" received in March 2010 for a period of 5 years. The QTRAP LC-MS/MS instrument offers unmatched qualitative performance for proteomic, peptidomic and drug discovery, as well as the wide dynamic range required for accurate quantitation central to our research activities. Furthermore, the instrument proposed is needed to quantify protein expression using multiplexed isobaric tagging technology and specific multiple reaction monitoring (MRM) into experimental animal models of chronic and neuropathic pain. MRM techniques are the gold standard in quantitative biomarkers discovery and validation. The performance of protein and peptide quantification methods is important in biomarker research since it is used to determine protein expression, performed principal component analysis (PCA) and define valid multiparametric profiles for diagnostic and prognostic purposes. Additionally, these types of instrument are an excellent choice to perform quantification of drug and metabolites in complex biological matrices. Drug pharmacokinetic and metabolism are key elements of animal pharmacology research and an integral part of our highly qualified scientists training program in biomedical research. The acquisition of the QTRAP LC-MS/MS will significantly contribute to our effort to develop new mechanistic knowledge of pain transmission, identify specific biomarkers and foster the basis for the development of innovative pain therapies. This new LC-MS/MS will have an immediate impact into our research activities and the training of Highly Qualified Personnel (HQP).