Analytic Core

分析核心

• 批准号: 10062146
• 负责人: NICHOLAS H. OBERLIES
• 金额: $ 75.23万
• 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/10062146
• 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; 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 warehouse; 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.

分析核心项目总结 研究植物和其他天然产物（NP）的一个核心挑战是它们固有的复杂性， 可变性与传统药物不同，NP是混合物，其化学组成不完全已知， 可能会有所不同，这取决于源材料的遗传学以及它们如何生长和加工。除非 仔细考虑，这种变异性可能混淆NP的体外和临床研究。总体 分析核心的目标是支持我们中心的严格和可重复的相互作用研究， 天然产物药物相互作用研究卓越奖（NaPDI中心）。这一奋进的关键将是 确保NP研究材料真实（正确识别属和种），无污染物，以及 良好表征的剂量性能和稳定性。研究材料将从商业上选择 我们的产品经过仔细考虑消费者趋势、化学成分和产品质量后，另一 分析核心的重要功能是提供具有确定结构的分离的NP成分， 纯度，以支持药理学核心进行的体外机制研究。最后，我们将 与药理学核心量化目标药物/代谢物，NP成分和药物代谢 从临床NP-药物相互作用获得的药代动力学样本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本报告期间建立的方法来实现。 供资周期，包括目标定量液相色谱和质谱的应用 方法和非靶向质谱代谢组学。我们严格的工作流程最近发表在 高影响力的评论文章在天然产品报告。为《公约》提出的研究的一个创新方面是： 更新应用将是使用代谢组学来表征肠吸收的成分， 复杂的NP这些研究将使用已建立的人肠体外模型（Caco-2细胞）进行 单层）和通过表征从临床NPDI获得的人样品（血浆、尿液和粪便） 由药理学中心进行的研究。重要的是，研究中产生的研究结果 将通过信息学核心专门设计的定制门户网站共享， 向研究界传播NaPDI中心生成的数据。分析核心由一个团队组成， 在研究合作方面有着广泛记录的科学家，包括多篇合著的出版物 与药理学核心和信息学核心的研究者发表的NPDI研究相关。的 分析核心研究人员的集体天然产物化学和生物分析专业知识确保 实现为该核心文件设定的里程碑，从而帮助推进对国家政策和行动指示的理解 及其临床意义。