Analytic Core

分析核心

• 批准号: 10471292
• 负责人: NICHOLAS H. OBERLIES
• 金额: $ 90.35万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471292
• 关键词: Address; American; Biological Markers; Black Pepper; Botanicals; Caco-2 Cells; Cannabis sativa plant; Chemicals; Cinnamomum; Cinnamon - dietary; Clinical; Clinical Research; Collaborations; Communities; Complex; Complex Mixtures; Consumption; Custom; Data; Drug Interactions; Drug Kinetics; Drug Prescriptions; Echinacea Preparation; Echinacea purpurea; Education; Educational workshop; Ensure; Enzymes; Feces; Funding; Genetic; Goals; Goldenseal; Health; Hemp; Human; In Vitro; Informatics; Intestinal Absorption; Intestines; Investigation; Leadership; Mass Spectrum Analysis; Methodology; Methods; Mission; Mitragyna; Modeling; Monitor; Natural Product Drug; Natural Products; Natural Products Chemistry; Participant; Peer Review; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Piper nigrum; Plasma; Preparation; Process; Publications; Publishing; Reporting; Reproducibility; Research; Research Personnel; Safety; Sales; Sampling; Scientist; Services; Source; Structure; Testing; Urine; Work; Xenobiotics; absorption; clinically relevant; clinically significant; data repository; design; dietary supplements; dosage; drug disposition; experience; in vitro Model; innovation; liquid chromatography mass spectrometry; metabolomics; method development; monolayer; research study; symposium; trend

PROJECT SUMMARY OF THE ANALYTICAL CORE A central challenge in studying botanical and other natural products (NPs) is their inherent complexity and variability. Unlike conventional drugs, NPs are mixtures, for which chemical composition is not fully known and may vary depending on the genetics of the source material and how they are grown and processed. Unless it is carefully accounted for, such variability can confound in vitro and clinical studies of NPs. The overarching objective of the Analytical Core is to support rigorous and reproducible Interaction Studies for our Center of Excellence for Natural Product Drug Interaction Research (NaPDI Center). Critical to this endeavor will be ensuring that NP study material is authentic (genus and species correctly identified), free of contaminants, and well-characterized for dosage performance and stability. Study material will be chosen from commercially available products with careful consideration of consumer trends, chemical profile, and product quality. Another important function of the Analytical Core will be to provide isolated NP constituents with defined structure and purity in support of mechanistic in vitro studies to be conducted by the Pharmacology Core. Finally, we will work with the Pharmacology Core to quantify object drugs/metabolites, NP constituents, and drug metabolizing enzyme and transporter biomarkers in pharmacokinetic samples obtained from clinical NP-drug interaction (NPDI) studies. These goals will be accomplished by employing methodologies established during the current funding cycle, including application of both targeted, quantitative liquid-chromatography and mass spectrometry methods and untargeted mass spectrometry metabolomics. Our rigorous workflow was recently published in a high impact review article in Natural Product Reports. An innovative aspect of the studies proposed for the renewal application will be the use of metabolomics to characterize the intestinal absorption of constituents from complex NPs. These studies will be conducted using an established human intestinal in vitro model (Caco-2 cell monolayers) and by characterizing human samples (plasma, urine, and feces) obtained from clinical NPDI studies conducted by the Pharmacology Core. Importantly, the research findings generated in studies conducted by the Analytical Core will be shared via a customized portal designed by the Informatics Core specifically to disseminate NaPDI Center-generated data to research communities. The Analytical Core consists of a team of scientists with an extensive track record in research collaboration, including multiple co-authored publications relevant to NPDI studies published with investigators from the Pharmacology Core and Informatics Core. The collective natural products chemistry and bioanalytical expertise of the Analytical Core investigators ensures accomplishment of the milestones set forth for this Core, thereby helping to advance the understanding of NPDIs and their clinical relevance.

分析核心的项目摘要 研究植物和其他天然产品（NP）的核心挑战是它们固有的复杂性， 可变性。与常规药物不同，NP是混合物，为此，化学成分尚不完全知道，并且 可能会根据原始材料的遗传学以及它们的生长和处理方式而有所不同。除非是 仔细考虑的，这种变异性会在体外和NP的临床研究中混淆。总体 分析核心的目的是为我们的中心支持严格且可重复的相互作用研究 自然产品互动研究卓越（NAPDI中心）。这项工作至关重要 确保NP研究材料是真实的（正确识别的属和物种），没有污染物，并且 特征良好的剂量性能和稳定性。研究材料将从商业上选择 可仔细考虑消费者趋势，化学概况和产品质量的可用产品。其他 分析核心的重要功能将是提供具有确定结构的孤立的NP成分， 纯度以支持药理学核心进行的机械体外研究。最后，我们将工作 用药理学核心来量化对象药物/代谢产物，NP成分和药物代谢 从临床NP-rug相互作用获得的药代动力学样品中的酶和转运蛋白生物标志物 （NPDI）研究。这些目标将通过采用当前建立的方法来实现 融资周期，包括针对目标的定量液态色谱和质谱法的应用 方法和未靶向的质谱代谢组学。我们严格的工作流程最近发表在 自然产品报告中的高影响评论文章。为研究提出的研究的创新方面 更新应用将是使用代谢组学来表征来自 复杂的NP。这些研究将使用已建立的人肠内体外模型（Caco-2细胞）进行 单层）并通过表征从临床NPDI获得的人类样品（血浆，尿液和粪便） 药理学核心进行的研究。重要的是，进行的研究中产生的研究结果 通过分析核心将通过专门针对信息核心设计的自定义门户来共享 将NAPDI中心生成的数据传播到研究社区。分析核心由一个团队组成 在研究合作方面拥有广泛记录的科学家，包括多个合着的出版物 与药理学核心和信息学核心的研究人员发表的NPDI研究相关。这 分析核心研究人员的集体天然产品化学和生物分析专业知识确保 为此核心提出的里程碑的完成，从而有助于提高对NPDIS的理解 以及他们的临床意义。