Research Project
10254444
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.
