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，购买一台三重四极杆质谱仪，以取代现有的已有9年历史的Waters MicroMassQuattro LC仪器。这笔资金将用于购买应用生物系统公司(AB)的SCIEX Triple QuadTM 5500(API 5500)系统(串联式四极质谱计)和ACQUITY UPLCTM色谱系统，该系统将专门用于支持需要灵敏定量分析的NIH资助的研究人员。约翰斯·霍普金斯医疗机构的9名研究人员(4名主要研究人员，5名次要研究人员)的研究(100%由美国国立卫生研究院资助)依赖于只能使用所要求的仪器进行的分析。约翰霍普金斯大学基梅尔癌症中心(JHU KCC)是1976年以来由NCI指定的综合性癌症中心，是约翰霍普金斯大学医学研究所的一部分，该研究所获得了临床和翻译研究所(卢旺达问题国际法庭)奖。JHU KCC分析药理学核心(JHU KCC APC)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。卢旺达问题国际法庭已向非癌症中心成员扩大了使用JHU KCC APC的机会，JHU KCC APC得到了NIH资助的赠款的大量使用，这些赠款支持I期试验(U01)和临床前研究项目(例如，塔西卡林前体药物的临床前开发(R01)、干酪性肉芽肿药物(R01)和布鲁里溃疡药物(R01)的临床前开发)。由于JHU KCC APC支持抗癌药物的早期临床开发和临床前癌症相关研究，它是癌症中心和约翰·霍普金斯医疗机构的关键资源。这一关键资源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。由于Waters Corporation将在2009年末停止为该仪器提供服务合同和更换部件，因此，除非在MicroMassQuattro LC完全退役之前，我们实验室中已有合格的新质谱仪投入使用，否则JHU KCC APC的容量将大幅下降(50%)。添加新的LC/MS/MS以取代过时的LC/MS/MS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，它还将通过在现有LC/MS/MS上腾出时间间接受益于NIH资助的合同和研究。JHU KCC APC的LC/MS/MS能力将有助于约翰霍普金斯大学医疗机构的长期生物医学研究目标。 与公共卫生相关：能够以高灵敏度和高选择性对细胞、血浆和组织中的药物及其代谢物进行量化是旨在改进疾病治疗或了解生物过程的基本机制的研究项目的基本需要。拟议更新的分析仪器将为约翰·霍普金斯医疗机构带来必要的最先进的仪器，从而推动许多旨在改善癌症和结核病等严重疾病治疗的项目。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to acquire funds to purchase a triple quadrupole mass spectrometer to replace an existing 9-year old Waters Micromass Quattro LC instrument. The funds will be used to purchase a Applied Biosystems (AB) SCIEX Triple QuadTM 5500 (API 5500) system (a tandem quadrupole mass spectrometer) coupled with an ACQUITY UPLCTM chromatographic system that will be dedicated to support NIH-funded investigators requiring sensitive quantitative analysis. A group of 9 investigators at the Johns Hopkins Medical Institutions (4 major, 5 minor) has been identified whose research (100% NIH-funded) is dependent on analyses which are only possible with the requested instrument. The Johns Hopkins University Kimmel Cancer Center (JHU KCC) is a NCI-Designated Comprehensive Cancer Center since 1976 and is part of the Johns Hopkins Medical Institute which has the Institute for Clinical and Translational Research (ICTR) Award. The JHU KCC Analytical Pharmacology Core (JHU KCC APC) 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. The ICTR has broadened access to the JHU KCC APC to non-Cancer Center members, The JHU KCC APC is used heavily by NIH-funded grants supporting both Phase I trials (U01),and preclinical research projects (e.g., preclinical development of thapsigargin prodrugs (R01), agents in Caseating Granulomas (R01), and agents in Buruli ulcers (R01)). As the JHU KCC APC supports both early clinical development of anti-cancer drugs and pre-clinical cancer-related research, it is a critical resource for the Cancer Center and the Johns Hopkins Medical Institutions. This critical resource 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. As Waters Corporation is terminating the Micromass Quattro LC product line, by ceasing to provide service contracts and replacement parts for this instrument in late 2009, the capacity of the JHU KCC APC will decrease substantially (50%) unless a qualified new mass spectrometer is functionally up and running in our laboratory prior to the Micromass Quattro LC being fully decommissioned. The addition of a new LC/MS/MS to replace the outdated LC/MS/MS will directly benefit NIH grant-funded early clinical and preclinical 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 LC/MS/MS capability of the JHU KCC APC will contribute to the long-range biomedical research goals of the Johns Hopkins Medical Institutions. PUBLIC HEALTH RELEVANCE: The ability to quantify drugs and their metabolites in cells, plasma, and tissues with high sensitivity and selectivity is an essential need of research projects that aim to improve the therapy of diseases or to understand the basic mechanisms of biological processes. The proposed updated analytical instrument will bring the state-of-the-art instrumentation necessary to the Johns Hopkins Medical Institutions, thereby advancing many projects that seek to improve the therapy of serious diseases such as cancer and tuberculosis.