Bioanalytical Core

项目摘要--生物分析核心 生物分析核心实验室将提供最先进和创新的生物分析专业知识和 药物及其代谢物、内源性化学物质和其他分子的定量技术 在与中心其他核心和所有资助药物的新合作研究中的生物学意义 虐待这所大学和邻近大学的生物医学研究人员。这些分析将提供专业知识，以 进行新的和创新的研究，并以意想不到的方式加强目前获得资助的研究项目 在他们提交申请时。此核心将通过使可用可靠、 用于新项目的生物和非生物材料的有效质谱分析 NIH赞助和其他研究人员研究滥用物质和成瘾的作用机制。 该实验室将开发专注于在生物标本中鉴定和定量的方法 药物和/或药物代谢物，如可卡因、尼古丁、可替宁、四氢大麻酚(THC)，以及 出现的精神活性化合物，如荷叶碱、阿朴吗啡和三尖杉碱，以及生理上的 活性内源性小分子和/或其代谢物，如花生胺、其他内源性大麻素、 鞘磷脂的前胺和神经酰胺代谢物。这些分析将加强 滥用药物的药理学研究通过提供包括药物处置在内的药代动力学分析， 新陈代谢和清除。生物分析核心将以最少的成本开发新的创新技术 可快速分离和定量极性药物代谢物和葡萄糖醛酸苷的样品制备 代谢物。我们将扩展小分子类型的广度，包括其他滥用物质 特制药物(即合成阿片类药物、拟大麻药物和卡西诺酮)及其代谢物，范围更广 与滥用药物具有相似药理作用的内源性化合物包括 内源性大麻素、多肽、脂类和其他生物递质或信号化合物。我们还将 通过差分离子迁移率质谱仪(DMS)增强选择性能力，使我们能够提高 我们对同压化合物的量化，识别以前从未见过的代谢物，以及感兴趣的离子的分离 受干扰离子的影响。结合微萃取/样品制备技术和/或二维 色谱分离与质谱仪(MS)相结合，DMS的选择性能力，将提供 本校园和我们学校的所有药物滥用研究人员提出的研究的新维度 邻近的机构。

Project Summary – Bioanalytical Core The Bioanalytical Core Laboratory will provide state of the art and innovative bioanalytical expertise and techniques for the quantification of drugs and their metabolites, endogenous chemicals and other molecules of biological significance in new collaborative studies with the other cores in the center and all the funded drug abuse biomedical researchers at this and neighboring universities. These analyses will provide the expertise to perform new and innovative research and to enhance currently funded research projects in ways not anticipated at the time of their application submission. This core will accomplish these goals by making available reliable, validated mass spectrometric analysis of biological and non-biological materials for new projects as well as for NIH sponsored and other researchers studying the mechanism of action of abused substances and addiction. The laboratory will develop methods focused on the identification and quantification in biologic specimens of drugs and/or drug metabolites, such as cocaine, nicotine, cotinine, tetrahydrocannabinol (THC), and, natural occurring psychoactive compounds such as nuciferine, apomorphine and mitragynine, as well as physiologically active small endogenous molecules and/or their metabolites such as anandamide, other endocannabinoids, prostamides and ceramide metabolites of sphingomelingolipids. These analyses will enhance the pharmacological studies of drugs of abuse by providing pharmacokinetic analysis including drug disposition, metabolism and clearance. The Bioanalytical Core will develop novel and innovative techniques for minimum sample preparation to allow rapid isolation and quantification of polar drug metabolites and glucuronide metabolites. We will expand on the breadth of types of small molecules including additional substances of abuse designer drugs (i.e., synthetic opioids, cannabimimetic, and cathinones), and their metabolites, a wider range of endogenous compounds which have similar pharmacological effects as drugs of abuse including endocannabinoids, peptides, lipids and other biological transmitters or signaling compounds. We will also enhance selectivity capabilities with differential ion mobility mass spectrometry (DMS) allowing us to increase our quantification of isobaric compounds, identify metabolites not seen before, and separation of ions of interest from interfering ions. Incorporating micro-extraction/sample preparation technologies and/or two-dimensional chromatographic separations combined with mass spectrometry (MS), DMS selectivity capability, will provide new dimensions to the research proposed of all drug abuse researchers on this campus and those in our neighboring institutions.