Liquid Chromatography Tandem Mass Spectrometry

描述（由申请人提供）：位于港-加州大学洛杉矶分校医学中心的洛杉矶生物医学研究所（LA Biomed）一般临床研究中心（GCRC）正在申请用于GCRC核心实验室和生物医学质谱设备的液相色谱串联质谱仪（LC-MS/MS）。要求LC/MS/MS服务于port - la Biomed和我们在洛杉矶的姐妹机构（Cedars Sinai医学中心（Cedars-Sinai）， UCLA-Westwood和Charles Drew健康与科学大学（Drew））的临床和转化研究人员的需求。共享该设备的服务是我们准备在四个姐妹机构之间联合申请临床和转化科学研究所（CTSI）的重要组成部分。为了避免重复，提高效率和优化实验室的利用，加州大学洛杉矶分校西木分校、雪松西奈分校、港湾-洛杉矶生物医学中心和德鲁分校的GCRC项目和实验室主任同意将港湾-加州大学洛杉矶分校GCRC核心实验室和生物医学质谱设备指定为所有四个CTSI机构的中央内分泌和代谢核心实验室。目前，GCRC核心实验室主要通过免疫分析提供激素和维生素分析。与LC/MS/MS相比，这些方法具有较高的方差，较差的再现性，并且在许多情况下准确性较低。临床小分子检测在研究中面临的挑战包括高灵敏度和低定量限（LOQ）到低毫纳范围的要求。这种敏感性是必要的，以便能够准确诊断激素或维生素缺乏症，并监测男子、妇女和儿童的治疗情况。我们目前的研究人员包括6个主要的NIH用户，15个协议，9个NIH资助用户和6个其他初级和资助的研究人员。这些研究人员从事广泛的研究，包括儿童和老年人的代谢性骨病，男性和女性的激素缺乏，激素和非激素依赖性癌症，艾滋病毒疾病的合共病，以及重要的是，了解这些疾病的机制。随着验证分析组合的扩大，我们预计我们可以支持两倍以上的研究方案。这项申请得到了所有四所参与院校的大力支持。提供质谱技术能力的核心设施的加强也将大大提高我们的服务能力，不仅是我们的机构，还有我们在加州大学洛杉矶分校、西达斯-西奈和南加州德鲁的姐妹机构，以及我们多样化的、经常得不到服务的患者群体。公共卫生相关性：港-加州大学洛杉矶分校一般临床研究中心正在申请最先进的高通量液相色谱串联质谱计的资助，以测量人体体液中的血清激素和其他代谢产物。这将允许测量非常少量的这些激素和化学物质具有非常高的选择性，准确性和精密度。该方法的应用将支持来自洛杉矶生物医学中心、雪松西奈、加州大学洛杉矶分校韦斯特伍德和德鲁大学的许多研究人员，为我们服务不足的人群诊断和监测许多代谢、内分泌、肾脏和骨骼疾病的治疗。

DESCRIPTION (provided by applicant): The Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA Biomed) General Clinical Research Center (GCRC) is applying for a Liquid Chromatography Tandem Mass Spectrometer (LC-MS/MS) for the GCRC Core Laboratory and the Biomedical Mass Spectrometry Facility. The LC/MS/MS is requested to serve the needs of clinical and translational investigators at Harbor-LA Biomed and our sister institutions in Los Angeles (Cedars Sinai Medical Center (Cedars-Sinai), UCLA-Westwood, and the Charles Drew University of Health and Science (Drew)). The sharing of the services of this equipment is an important part of our preparation for a joint application for a Clinical and Translational Sciences Institute (CTSI) across the four sister institutions. To avoid duplication, increase efficiency and optimize utilization in the laboratory, the program and laboratories directors of the GCRCs at UCLA Westwood, Cedars-Sinai, Harbor-LA Biomed and Drew have agreed to designate the Harbor-UCLA GCRC Core Lab and Biomedical Mass Spectrometry facility as the central Endocrine and Metabolism Core Laboratory for all four CTSI institutions. Currently, the GCRC Core Laboratory provides hormone and vitamin analyses mostly by immunoassays. These methodologies have higher variance, poorer reproducibility and in many instances less accuracy than that obtained from LC/MS/MS. The challenges of clinical assays of small molecules in research include the requirements of high sensitivity and low limit of quantitation (LOQ) into the low fentomolar range. Such sensitivity is necessary in order to be able to accurately diagnose hormonal or vitamin deficiency and to monitor its treatment in men, women and children. Our current investigators include 6 major NIH users with 15 protocols, 9 NIH funded users and 6 other junior and funded investigators. These investigators are engaged in a wide spectrum of research spanning from metabolic bone diseases inflicting children and the elderly, hormonal deficiencies in men and women, hormone and non-hormone dependent cancers, co-morbidities of HIV disease and importantly, understanding mechanisms underlying these diseases. With expansion of validated assay portfolio we anticipate that we can support more than twice the research protocols. This application is strongly supported by all four participating institutions. The strengthening of the Core Facilities providing Mass Spectrometry Technology capability will also significantly enhance our ability to serve not only our institution but our sister institutions at UCLA, Cedars-Sinai, and Drew in Southern California and our diverse and often underserved patient population. PUBLIC HEALTH RELEVANCE: The Harbor-UCLA General Clinical Research Center is requesting the funding of a state of the art, high-throughput liquid chromatography tandem mass spectrometer to measure serum hormones and other metabolic products in human bodily fluids. This will allow the measurement of very small amounts of these hormones and chemicals with very high selectivity, accuracy and precision. The application of this method will support many investigators from LA BioMed, Cedars-Sinai, UCLA-Westwood and Drew University in the diagnosis and monitoring of treatment of many metabolic, endocrine, kidney an bone disease for our underserved population.