Analytic Core

分析核心的项目摘要 研究植物学和其他天然产物(NP)的一个中心挑战是它们固有的复杂性和 可变性。与传统药物不同，纳米粒是一种混合物，其化学成分尚不完全清楚， 可能会有所不同，这取决于原始材料的遗传以及它们是如何生长和加工的。除非它是 仔细考虑，这种变异性可能会混淆NPs的体外和临床研究。最重要的是 分析核心的目标是为我们的中心支持严格和可重现的交互研究 天然产物药物相互作用研究杰出奖(NaPDI中心)。对这一努力至关重要的是 确保NP研究材料是真实的(正确识别属和种)，没有污染物，以及 在用量、性能和稳定性方面具有良好的特性。学习材料将从商业上选择 在仔细考虑消费者趋势、化学成分和产品质量的情况下，提供可用的产品。另一个 分析核心的重要功能将是提供具有明确结构和 纯度支持药理学核心将进行的机械性体外研究。最后，我们将努力 利用药理学核心对目标药物/代谢物、NP成分和药物代谢进行量化 临床NP-药物相互作用药代动力学样品中的酶和转运体生物标志物 (NPDI)研究。这些目标将通过采用本年度建立的方法来实现 供资周期，包括靶向、定量液相色谱和质谱法的应用 方法和非靶向质谱仪代谢组学。我们严格的工作流程最近发表在 天然产品报告中的高影响力评论文章。建议的研究的一个创新方面 新的应用将是使用代谢组学来表征来自于 复杂的NP。这些研究将使用已建立的人体肠道体外模型(Caco-2细胞)进行 单层)，并通过表征从临床NPDI获得的人体样本(血浆、尿液和粪便) 药理学核心所进行的研究。重要的是，在进行的研究中产生的研究结果 将通过由Informatics Core专门设计的定制门户共享 将NaPDI中心生成的数据传播给研究社区。分析核心由以下团队组成 在研究合作方面有广泛记录的科学家，包括多篇合著出版物 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。这个 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 完成为这一核心规定的里程碑，从而有助于促进对国家发展指标的理解 以及它们的临床相关性。

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.