Applied Biosystems API5500 Triple Quadrupole Mass Spectrometer

描述(申请人提供)：艾滋病毒/艾滋病、结核病、疟疾和锥虫病是对国际卫生具有重大意义的传染病，对全球人口造成巨大的疾病负担。艾滋病毒是国际上最大的死亡原因，是一种具有致命后果和疫苗预防前景黯淡的大流行病。结核病是第二大致死原因，存在于世界各地，并在许多流行地区流行，在这些地区，结核病的流行率很高，死亡率很高。疟疾和锥虫病在世界上一些资源最有限的国家造成了巨大的困难。在这项提议中，7名由美国国立卫生研究院资助的有资格的研究人员与另外5名受资助的研究人员一起致力于这4个主要国际卫生问题的治疗或预防的研究工作。要做到这一点，我们需要强大的最先进的LC-MS/MS仪器，专门用于检测和定量低皮摩尔到毫微摩尔水平的治疗性抗感染药物。申请资金用于购买一个应用生物系统API5500 LC-MS/MS系统，该系统具有Water Acquity UPLC接口，具有电喷雾电离(ESI)和大气压化学电离(APCI)能力。增加这一质谱仪系统将为合格的调查人员提供充分的机会，这些调查人员目前获得的可接受仪器极其有限或无法获得，或者目前的化验承诺超出了他们的能力。收购成本为350,350美元；对其适当住房和生产性使用的机构支持是强有力的。定量LC-MS/MS多反应监测(MRM)技术将提供与用于或正在评估这些疾病的抗感染药物的治疗水平、药代动力学和代谢相关的关键数据。所要求的仪器的供应将大幅增加样品吞吐能力，将支持新的研究计划，将允许在多台仪器上从分析开发到样品分析的无缝过渡，并将提供一种备份机制，以防止在仪器故障的情况下丢失宝贵的临床样品。尽管这些疾病的发病率、死亡率和经济负担被广泛认为是巨大的，但新的治疗进展往往落在NIH赞助的学术科学家身上。所要求的仪器的提供将大大提高约翰霍普金斯大学这些研究人员的工作效率。 公共卫生相关性：需要申请的API5500质谱仪，以支持由美国国立卫生研究院资助的科学家的研究，这些科学家正在努力开发艾滋病毒、结核病、疟疾和非洲锥虫病的新预防和治疗方法。这种仪器的使用将极大地提高他们在实验室研究和临床试验中研究新的治疗方法的能力。

DESCRIPTION (provided by applicant): HIV/AIDS, tuberculosis (TB), malaria and trypanosomiasis are infectious diseases of major importance to international health causing tremendous disease burdens on populations globally. HIV, the greatest cause of death internationally, is pandemic with fatal outcomes and dim prospects for vaccine prevention. TB, the second greatest cause of death, exists throughout the world and is epidemic in many regions where its prevalence is great and its mortality is common. Malaria and trypanosomiasis cause immense hardship in some of the world's most resource-limited countries. In this proposal seven established and qualifying NIH-funded investigators are joined by 5 other funded investigators to focus research efforts on the treatment or prevention of these 4 major international health problems. To do so, we require robust state-of-the-art LC-MS/MS instrumentation dedicated to detection and quantitation of low picomolar to femtomolar levels of therapeutic anti-infectives. Funding is requested for purchase of one Applied Biosystems API5500 LC-MS/MS system with a Water Acquity UPLC interface with capabilities for electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). The addition of this mass spectrometer system will provide adequate access to qualified investigators that currently have either extremely limited or no access to acceptable instrumentation or currently have assay commitments that exceed their capacity. The acquisition cost is $350,350; institutional support for its proper housing and productive use is robust. Quantitative LC-MS/MS multiple reaction monitoring (MRM) techniques will provide critical data related to therapeutic levels, pharmacokinetics and metabolism of anti-infectives employed or being evaluated for these diseases. The availability of the requested instrumentation will provide a substantial increase in sample throughput capacity, will support new research initiatives, will allow the seamless transition from assay development to sample analysis on more than one instrument, and will provide a back-up mechanism that prevents loss of precious clinical samples in the event of an instrument failure. Despite the morbidity, mortality and economic burden of these diseases, which are widely recognized to be enormous, new therapeutic advances often fall to NIH-sponsored academic scientists. The availability of the requested instrument would substantially increase the productivity of these investigators at Johns Hopkins. PUBLIC HEALTH RELEVANCE: The requested API5500 mass spectrometer is needed to support the NIH-funded research of scientists who are working to develop new preventions and treatments for HIV, tuberculosis, malaria and African trypanosomiasis. The availability of this instrument will greatly increase their ability to study new therapeutic approaches in laboratory studies and in clinical trials.