Ultra-performance liquid chromatography - triple quadrupole mass spectrometry system

项目摘要 亚利桑那大学正在申请资金用于购买超高效液相色谱仪 - 三重四极杆质谱系统（三重四极杆UPLC/MS）。仪器将被操作 在亚利桑那大学癌症中心的框架内，分析化学共享资源（UACC， ACSR）支持12名NIH资助的研究人员，包括10名UACC研究人员和新用户。ACSR是一种 自2001年以来，UACC癌症中心支持补助金（CCSG）资助的共享资源， 支持进行基于色谱-质谱的分析，以定量测量 药物、新型治疗剂、营养品、生物活性食品成分、致癌物、有毒物和内源性 各种生物样本中的代谢物，以及非靶向代谢组学的定性研究， 脂质组学它在为UACC调查人员和校园范围内的用户提供支持方面有着良好的记录， 在国家癌症研究所的CCSG审查中获得了“杰出”的荣誉。在此列出的用户 申请人过去和/或正在进行的项目由ACSR支持。三重四极杆LC/MS是 被认为是快速开发、验证和实施分析化学的黄金标准 能够对复合物中的小分子分析物进行高灵敏度和特异性定量分析的测定 生物样本仪器的主要需求是更换老化仪器（Quantum Ultra三重 2005年收购的quad）不再受制造商支持。艺术与建筑策略检讨所资助的项目平均 每年有30名调查人员，今天仍在使用这种老化的设备来支持大约40%的项目。在 除了更换老化的仪器外，所要求的仪器还提供了改进的测定灵敏度 进入PPT范围和超出范围，并且具有更宽的质量范围，扩展了肽的分析。随着 扫描速度与动态多反应监测相结合，所要求的仪器还可以支持 全面、高通量、靶向脂质组学分析。最后，升级后的UPLC将增强 与我们目前的系统相比，通过缩短运行时间和上级分离，提高了性能和容量。的 该仪器将支持评估新型治疗剂的全身生物利用度和组织分布 和预防性干预措施，测量全身和靶组织致癌物/毒物的程度 暴露，测量生物液体和组织中的内源性代谢物作为替代风险和/或终末- 点生物标志物，并用于评估代谢变化，以确定疾病的潜在机制， 并开发新的治疗策略。将所要求的仪器放入井内─ 建立共享资源将提高成本效益，鼓励用户之间的最佳共享，并促进 多学科协作环境。我们坚信，所要求的文书将具有 对亚利桑那大学NIH资助的基础、转化和临床研究产生重大影响， 有助于该机构在生物医学研究方面的持续成功。

PROJECT SUMMARY The University of Arizona is requesting funds for the acquisition of an ultra-performance liquid chromatography – triple quadrupole mass spectrometry system (triple quadrupole UPLC/MS). The instrument will be operated within the framework of the University of Arizona Cancer Center, Analytical Chemistry Shared Resource (UACC, ACSR) to support 12 NIH-funded researchers, including 10 UACC investigators, and new users. ACSR is a shared resource funded by the UACC Cancer Center Support Grant (CCSG) since 2001 to provide centralized support in performing chromatography-mass spectrometry based assays for quantitative measurements of drugs, novel therapeutics, nutraceuticals, bioactive food components, carcinogens, toxicants, and endogenous metabolites in various biological specimens, as well as qualitative studies in untargeted metabolomics and lipidomics. It has a proven track record of providing support to UACC investigators and campus-wide users and has received an “Outstanding” merit in the National Cancer Institute’s CCSG review. Users listed in this application have past and/or ongoing projects supported by the ACSR. The triple quadrupole LC/MS is considered the gold standard for rapid development, validation, and implementation of analytical chemistry assays to enable highly sensitive and specific quantitative analysis of small molecule analytes in complex biological samples. The primary need for the instrument is to replace an aging instrument (Quantum Ultra triple quad acquired in 2005) no longer supported by the manufacturer. ACSR supports projects from an average of 30 investigators annually and is still using this aging equipment today to support roughly 40% of projects. In addition to replacing the aging instrument, the requested instrument also offers an improved assay sensitivity into the ppt range and beyond and has a wider mass range expanding the analysis of peptides. With the ultrahigh scan speeds combined with dynamic multiple reaction monitoring, the requested instrument can also support comprehensive, high-throughput, targeted lipidomics analysis. Finally, the upgraded UPLC will enhance both capability and capacity, via shorten run time and superior separation compared to our current system. The instrument will support the assessment of the systemic bioavailability and tissue distribution of novel therapeutics and preventive interventions, the measurements of the extent of systemic and target tissue carcinogen/toxicant exposure, the measurement of endogenous metabolites in biofluids and tissues as surrogate risk and/or end- point biomarkers and for assessment of metabolic changes to define the mechanisms underlying the disease of interest and to develop new strategies for treatment. Incorporation of the requested instrument into a well- established shared resource will promote cost effectiveness, encourage optimal sharing among users, and foster a collaborative multidisciplinary environment. We strongly believe that the requested instrument will have a significant impact on NIH-funded basic, translational, and clinical research at the University of Arizona and contribute to the institution’s continued success in biomedical research.