UPLC with Tandem MS for Sensitive Quantitative Analysis of Small Molecules

UPLC 与串联 MS 对小分子进行灵敏的定量分析

• 批准号: 7792803
• 负责人: MICHELLE A RUDEK
• 金额: $ 42.86万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-22 至 2011-04-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7792803
• 关键词: 9 year old; Antineoplastic Agents; Arts; Award; Biological Process; Biomedical Research; Cancer Center; Clinical; Clinical Investigator; Comprehensive Cancer Center; Contract Services; Contracts; Coupled; Development; Disease; Equipment; Funding; Goals; Grant; Granuloma; Institutes; Institution; Laboratories; Malignant Neoplasms; Medical; Minor; Pharmaceutical Preparations; Pharmacology; Phase I Clinical Trials; Plasma Cells; Prodrugs; Qualifying; Research; Research Personnel; Research Project Grants; Resource Sharing; Resources; Running; Services; System; Technical Expertise; Thapsigargin; Time; Tissues; Translational Research; Tuberculosis; Ulcer; United States National Institutes of Health; Universities; Update; Water; experience; improved; instrument; instrumentation; mass spectrometer; member; microbial alkaline proteinase inhibitor; pre-clinical; pre-clinical research; preclinical study; public health relevance; rapid growth; small molecule

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.

描述（由申请人提供）：本提案的总体目标是获得资金，用于购买三重四极杆质谱仪，以取代现有的使用9年的沃茨Micromass Quattro LC仪器。这笔资金将用于购买Applied Biosystems（AB）SCIEX Triple QuadTM 5500（API 5500）系统（串联四极杆质谱仪）以及ACQUITY UPLCTM色谱系统，该系统将专门用于支持NIH资助的需要灵敏定量分析的研究人员。已确定约翰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），他们的研究（100%由NIH资助）依赖于只有使用所要求的仪器才能进行的分析。约翰霍普金斯大学Kimmel癌症中心（JHU KCC）自1976年以来一直是NCI指定的综合癌症中心，是约翰霍普金斯医学研究所的一部分，该研究所拥有临床和转化研究所（ICTR）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。ICTR已经将JHU KCC APC的使用范围扩大到非癌症中心成员，JHU KCC APC被NIH资助的赠款大量使用，用于支持I期试验（U 01）和临床前研究项目（例如，毒胡萝卜素前药（R 01）、干酪化肉芽肿中的药剂（R 01）和布鲁里溃疡中的药剂（R 01）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，因此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LC/MS/MS仪器目前已满负荷使用。由于沃茨公司将于2009年底终止Micromass Quattro LC产品线，停止提供该仪器的服务合同和更换部件，因此JHU KCC APC的容量将大幅下降（50%），除非在Micromass Quattro LC完全退役之前，我们实验室的合格新质谱仪功能正常并运行。添加新的LC/MS/MS以取代过时的LC/MS/MS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LC/MS/MS上腾出时间来资助。JHU KCC APC的LC/MS/MS能力将有助于约翰霍普金斯医疗机构的长期生物医学研究目标。 公共卫生相关性：以高灵敏度和选择性定量细胞、血浆和组织中药物及其代谢物的能力是旨在改善疾病治疗或了解生物过程基本机制的研究项目的基本需求。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仪器，从而推进许多寻求改善癌症和结核病等严重疾病治疗的项目。

项目成果

A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination.

• DOI: 10.1002/pros.23024
• 发表时间: 2015-10
• 期刊: The Prostate
• 作者: Paller CJ;Rudek MA;Zhou XC;Wagner WD;Hudson TS;Anders N;Hammers HJ;Dowling D;King S;Antonarakis ES;Drake CG;Eisenberger MA;Denmeade SR;Rosner GL;Carducci MA
• 通讯作者: Carducci MA

The impact of bevacizumab on temozolomide concentrations in intracranial U87 gliomas.

• DOI: 10.1007/s00280-012-1867-1
• 发表时间: 2012-07
• 期刊: CANCER CHEMOTHERAPY AND PHARMACOLOGY
• 影响因子: 3
• 作者: Grossman, Rachel;Rudek, Michelle A.;Brastianos, Harry;Zadnik, Patti;Brem, Henry;Tyler, Betty;Blakeley, Jaishri O.
• 通讯作者: Blakeley, Jaishri O.

Paclitaxel inhibits post-traumatic recurrent laryngeal nerve regeneration into the posterior cricoarytenoid muscle in a canine model.

在犬模型中，紫杉醇抑制创伤后喉返神经再生为后环杓肌。

• DOI: 10.1002/lary.26058
• 发表时间: 2017
• 期刊: The Laryngoscope
• 作者: Park,AndreaM;Bhatt,NeelK;Paniello,RandalC
• 通讯作者: Paniello,RandalC

Metformin Protects Cells from Mutant Huntingtin Toxicity Through Activation of AMPK and Modulation of Mitochondrial Dynamics.

• DOI: 10.1007/s12017-016-8412-z
• 发表时间: 2016-12
• 期刊: NEUROMOLECULAR MEDICINE
• 影响因子: 3.5
• 作者: Jin, Jing;Gu, Hao;Anders, Nicole M.;Ren, Tianhua;Jiang, Mali;Tao, Michael;Peng, Qi;Rudek, Michelle A.;Duan, Wenzhen
• 通讯作者: Duan, Wenzhen

A robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of 5-azacytidine.

• DOI: 10.1002/bmc.3562
• 发表时间: 2016-03
• 期刊: Biomedical chromatography : BMC
• 作者: Anders NM;Wanjiku TM;He P;Azad NS;Rudek MA
• 通讯作者: Rudek MA