Liquid Chromatograph - Tandem Mass Spectrometer

描述（由申请人提供）： 这是对液相色谱-串联质谱（LC-MS/MS）仪器的请求，该仪器将由斯克里普斯研究所（TSRI）的五名研究者组成的主要用户组以及TSRI和邻近机构的研究者组成的次要用户组使用。所要求的LC-MS/MS将用于分析脑组织、体内脑微透析液和血浆中的神经活性肽、内源性大麻素和外源性药物及其代谢物。这些分析将直接推动目前由NIH资助的研究。LC-MS/MS的几个特点将促进主要和次要用户群体的研究。首先，质谱仪提供了一种形式的“通用检测”，其提供比通常通过电化学、分光光度或免疫测定检测方法提供的分子特异性大得多的分子特异性。第二，串联质谱仪（MS/MS）提供比单四极杆质谱仪高得多的信噪比和更高的分析物特异性，在复杂的生物基质中提供更低的定量限。第三，所要求的毛细管液相色谱（LC）系统大大提高了质量灵敏度，非常适合于小体积（< 10？l）含有极低分析物浓度（pM-nM）的样品，同时根据需要提供分析较大样品体积的灵活性。LC-MS/MS将被安置在TSRI的共用设施中，该设施配备用于立即安装仪器而无需翻新。TSRI对仪器的长期维护和运行做出了财务承诺，包括服务合同、供应和技术人员的支持。一名高素质的技术人员将提供用户培训和仪器维护，一个内部咨询委员会将确保主要用户群体内外的调查人员公平使用仪器。LC-MS/MS仪器将对主要用户组内的22个NIH资助的研究项目的成功完成和更新产生重大影响，其中包括单个R 01研究项目，两个NIH资助的研究中心和一个NIH资助的计划项目。重要的是，使用所要求的仪器收集的结果可能会对导致药物和酒精滥用，饮食失调，慢性疼痛和精神疾病（如焦虑和抑郁）的神经机制提供新的见解。 健康相关性：所要求的LC-MS/MS仪器将能够定量生物样品（包括脑微透析液）中极低水平的神经活性物质。这将直接影响超过22个NIH资助的研究项目的进展和成功。所要求的仪器收集的结果将提供新的见解的神经机制，有助于药物和酒精滥用，饮食失调，慢性疼痛和精神疾病，如焦虑和抑郁症。

DESCRIPTION (provided by applicant): This is a request for a Liquid Chromatography - tandem Mass Spectrometry (LC- MS/MS) instrument that will be utilized by a major user group of five investigators at The Scripps Research Institute (TSRI) and also by a minor user group of investigators from TSRI and neighboring institutions. The requested LC-MS/MS will be used for the analysis of neuroactive peptides, endogenous cannabinoids and exogenous drugs and their metabolites in brain tissue, in vivo brain microdialysates and plasma. These analyses will directly advance research that is currently funded by NIH awards. Several characteristics of the LC-MS/MS will facilitate the research of the major and minor user groups. First, mass spectrometers provide a form of "universal detection" that offers much greater molecular specificity than is typically provided through electrochemical, spectrophotometric or immunoassay detection methods. Second, tandem mass spectrometers (MS/MS) provide substantially higher signal-to-noise ratios and considerably greater analyte specificity than do single quadrupole mass spectrometers, providing substantially lower limits of quantitation in complex biological matrices. Third, the requested capillary liquid chromatography (LC) system substantially enhances mass sensitivity and is very well suited for the separation of small volume (< 10 ?l) samples containing extremely low analyte concentrations (pM - nM) while providing flexibility for analysis of larger sample volumes as needed. The LC-MS/MS will be housed in a shared facility at TSRI that is equipped for the immediate installation of the instrument without need of renovation. TSRI has made a financial commitment to the long-term maintenance and operation of the instrument inclusive of service contracts, supplies and support of the technical staff. A highly qualified technical staff will provide user training and instrument maintenance and an Internal Advisory Committee will assure equitable instrument use by investigators both within and outside the major user group. The LC- MS/MS instrument will have a major impact on the successful completion and renewal of 22 NIH-funded research projects within the major user group that include individual R01 research projects, two NIH-funded Research Centers and one NIH-funded Program Project. Importantly, the results gathered with the requested instrument are likely to provide novel insight into the neural mechanisms contributing to drug and alcohol abuse, eating disorders, chronic pain, and psychiatric disorders such as anxiety and depression. HEALTH RELEVANCE: The requested LC-MS/MS instrument will provide the ability to quantify very low levels of neuroactive substances in biological samples including brain microdialysates. This will directly impact the progress and success of more than 22 NIH-funded research projects. The results gathered with the requested instrument will provide novel insight into the neural mechanisms contributing to drug and alcohol abuse, eating disorders, chronic pain and psychiatric disorders such as anxiety and depression.