UPLC with Tandem MS for Sensitive Quantitative Analysis of Small Molecules

描述（由申请人提供）：本提案的总体目标是获得资金以购买液相色谱/串联四极杆质谱检测（LC-MS/MS）系统，用于分析正在研究的用于治疗、风险关联和预防癌症的新型药物和生物标志物。这笔资金将用于购买与ACQUITY UPLC（tm）色谱系统耦合的沃茨（r）Micromass（r）Quattro Premier（tm）XE串联四极杆质谱仪，新仪器将专门用于支持NIH资助的需要灵敏定量分析的研究人员。City of Hope（COH）是一家由美国国家癌症研究所（National Cancer Institute，简称NCI）指定的综合性癌症中心，提供最先进的临床和转化研究型癌症护理。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业知识，并获得大型设备，用于抗癌药物和相关化合物的定量分析。总体而言，APCF被大量用于支持I期试验和SWOG早期治疗试验的NCI资助的赠款，支持II期试验的NCI资助的合同，以及同行评审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，化学预防剂的临床前开发，化学和紫外线诱导的致癌机制的基础研究，RNA靶向治疗的临床前研究，以及新型Stat-signaling靶向治疗的评价。因此，APCF支持抗癌药物的早期临床开发和临床前癌症相关研究，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。购买第二个LC-MS/MS系统，专门用于支持NIH资助的研究，现在需要保持核心设施的最先进水平，并使我们能够继续充分服务于资助的研究人员和那些追求NIH资助。第二台LC-MS/MS的增加将直接使NIH资助的早期临床和临床前试验项目受益。此外，它将间接受益于NIH资助的合同和研究，这些合同和研究目前没有通过在现有的LC-MS/MS上腾出时间来资助。

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.