UPLC with Tandem MS for Sensitive Quantitative Analysis of Small Molecules

描述(由申请人提供)：这项提案的总体目标是获得资金，购买用于分析正在研究的新药物和生物标志物的LC-MS/MS系统，用于癌症的治疗、风险关联和预防。这笔资金将用于购买配备ACQUITY UPLC(Tm)色谱系统的Waters(R)MicroMass(R)Quattro Premier(Tm)XE串联四极质谱计，新仪器将专门用于支持需要进行灵敏定量分析的NIH资助的调查人员。希望之城(COH)作为NCI指定的综合癌症中心，提供最先进的基于临床和转化性研究的癌症护理。COH的分析药理学核心设施(APCF)是癌症中心的共享资源，为受资助的研究人员提供技术专长并访问大型设备，用于抗癌药物和相关化合物的定量分析。总体而言，APCF被NCI资助的赠款大量使用，这些赠款支持第一阶段试验和SWOG早期治疗试验，NCI资助的合同支持第二阶段试验，以及同行审查的内部癌症化疗方案。然而，该核心也支持大量与癌症相关的实验室研究项目，例如，化学预防药物的临床前开发，化学和紫外线诱导致癌机制的基础研究，RNA靶向治疗的临床前研究，以及新的Stat信号靶向治疗的评估。因此，APCF既支持抗癌药物的早期临床开发，也支持临床前的癌症相关研究，因此是癌症中心的关键资源。由于其对癌症中心的重要性，APCF经历了需要分析服务的基础和临床研究人员数量的快速增长。因此，现有的LC-MS/MS仪器目前已满负荷使用。现在需要购买第二个LC-MS/MS系统，专门用于支持NIH资助的研究，以保持核心设施的最先进水平，并使我们能够继续为资助的研究人员和那些寻求NIH资助的人提供充分的服务。第二个LC-MS/MS的增加将直接使NIH拨款资助的早期临床和临床前试验项目受益。此外，它还将通过腾出现有LC-MS/MS的时间，间接惠及NIH资助的合同和目前不是NIH资助的研究。新仪器将放置在APCF目前的实验室空间，并将利用现有的技术和行政监督。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to acquire funds to purchase a liquid chromatographic/tandem quadrupole mass spectrometric detection (LC-MS/MS) system for analysis of novel agents and biomarkers under investigation for the treatment, risk association, and prevention of cancer. The funds will be used to purchase a Waters(r) Micromass(r) Quattro Premier(tm) XE tandem quadrupole mass spectrometer coupled with an ACQUITY UPLC(tm) chromatographic system, and the new instrument will be dedicated to support NIH-funded investigators requiring sensitive quantitative analysis. The City of Hope (COH), as an NCI-designated Comprehensive Cancer Center, provides state-of-the-art clinical and translational research-based cancer care. The Analytical Pharmacology Core Facility (APCF) of the COH is a Cancer Center shared resource that provides funded investigators with technical expertise and access to large equipment for quantitative analysis of anticancer drugs and related compounds. Overall, the APCF is used heavily by NCI-funded grants supporting Phase I trials and SWOG Early Therapeutics trials, an NCI-funded contract supporting Phase II trials, as well as peer-reviewed in-house cancer chemotherapy protocols. However, the core also supports a large number of cancer-related laboratory research projects, e.g., pre-clinical development of chemopreventive agents, basic investigations into the mechanism of chemical and UV light induced carcinogenesis, pre-clinical studies of RNA-targeted therapies, and evaluations of novel Stat-signaling targeted therapies. Thus, the APCF supports both early clinical development of anticancer drugs and pre-clinical cancer-related research, and is therefore a critical resource for the Cancer Center. Because of its importance to the Cancer Center, the APCF has experienced a rapid growth in the number of basic and clinical investigators requiring analytical services. As a result, usage of the existing LC-MS/MS instrument is currently at full capacity. Acquisition of a second LC- MS/MS system dedicated solely to support NIH funded research is now required to maintain the core facility as state-of-the-art, and to allow us to continue to adequately serve both funded investigators and those in pursuit of NIH funding. The addition of a second LC-MS/MS will directly benefit the NIH grant-funded early clinical and pre-clinical trial projects. In addition, it will indirectly benefit NIH-funded contracts and studies that are not currently NIH funded by freeing time on the existing LC-MS/MS. The new instrument will be housed in the current APCF laboratory space and will take advantage of existing technical and administrative oversight.