LIQUID CHROMATOGRAPHY/MASS SPECTROSCOPY SYSTEM

在由本提案的9位共同研究者进行的10个nih支持的核心项目中，液相色谱/串联质谱（LC/MS-MS）增强的分析灵敏度、高通量和精确的分子质量测定将为这些项目提供必要的能力，因为这些项目普遍需要对药物、其体内代谢物或蛋白质和肽片段的生物样品进行快速和精确的定量。我们寻求获得最先进的LC/MS-MS仪器来支持和加强这些研究项目，并在基础分子生物化学方面开辟新的研究途径。该仪器将代表广泛地理区域内唯一可用的研究级LC/MS-MS。它将被整合到一个中央核心设施中，该设施将为从事基础和应用生物医学研究的集中研究人员提供这些服务，这些研究人员对LC/MS-MS功能有广泛的、可证明的需求。这种现代仪器的可用性将提供高通量分析能力和计算机控制的数据采集/管理，不仅可以通过消除更繁琐、劳动密集型和灵敏度较低的基于液相色谱（LC）的分析来提高生产率，而且还可以使任何现有仪器都无法实现的实验方法成为可能。此外，鉴于这些研究人员中的一些人在NIH正在进行的临床试验中，在MDS和药物滥用的药物治疗领域发挥的作用，获得这一仪器将对人类福祉产生直接影响。因此，这些现有的和潜在的研究能力将极大地增强大量现有的、悬而未决的和计划中的nih支持的范围和影响广泛的项目。

In ten NIH-supported core projects conducted by the nine co- investigators of this proposal, the enhanced analytical sensitivity, high- throughput, and precise molecular mass determination of Liquid Chromatography/Tandem Mass Spectroscopy (LC/MS-MS) would provide essential capabilities to enhance these projects, given the common need for rapid and precise quantitation from biological samples of pharmacologica1 agents, their in vivo metabolites, or fragments of proteins and peptides. We seek to acquire state-of-the-art LC/MS-MS instrumentation to support and enhance these research programs, as well as open new research avenues in basic molecular biochemistry. This instrument would represent the only research-grade LC/MS-MS available in a wide geographical area. It will be integrated into a central core facility, which would provide these services to a concentrated population of researchers engaged in basic and applied biomedical research who have extensive, demonstrable need for LC/MS-MS capabilities. The availability of this modem instrumentation, which would provide high- throughput analytical capabilities and computer-controlled data acquisition/management, would not only enhance productivity by eliminating more tedious, labor intensive, and less sensitive Liquid Chromatography (LC) -based assays, but would also make possible experimental approaches that are not feasible with any existing instrument. Furthermore, acquisition of this instrument would have a direct impact on human well-being, given the role of some of these investigators in ongoing clinical trials of the NIH, in the area of pharmacotherapy for MDS and drug abuse. Therefore, these existing and potential research capabilities will enhance greatly a substantial number of existing, pending, and planned NIH-supported projects of broad scope and impact.