title: Synthesis and quantitative analysis of plasma-targeted metabolites of catechin and epicatechin.
abstract: Grape seed polyphenolic extract (GSPE) rich in the flavan-3-ols (+)-catechin and (-)-epicatechin beneficially modulates Alzheimer's Disease phenotypes in animal models. The parent molecules in the extract are converted to a series of methylated and glucuronidated derivatives. To fully characterize these metabolites and establish a robust quantitative assay of their levels in biological fluids, we have implemented a partial synthetic approach utilizing chemical methylation followed by enzymatic glucuronidation. Liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy were used to assign unequivocal structures to the compounds. An analytical method using solid-phase extraction and LC-MS/MS in selective reaction monitoring mode (SRM) was validated for their quantitation in plasma. These studies provide a basis for improvements in future work on the bioavailability, metabolism, and mechanism of action of metabolites derived from dietary flavan-3-ols in a range of interventions.
authors: Department of Biological Sciences, University of North Texas , 1155 Union Circle #305220, Denton, Texas 76203-5017, United States.
authors: Jack W
authors: JW
authors: Blount
authors: Benjamin W
authors: BW
authors: Redan
authors: Mario G
authors: MG
authors: Ferruzzi
authors: Bradley L
authors: BL
authors: Reuhs
authors: Bruce R
authors: BR
authors: Cooper
authors: John S
authors: JS
authors: Harwood
authors: Vladimir
authors: V
authors: Shulaev
authors: Giulio
authors: G
authors: Pasinetti
authors: Richard A
authors: RA
authors: Dixon
mesh_terms: D000818:Animals; D002392:Catechin / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism; D056604:Grape Seed Extract / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats
chemical_list: D056604:Grape Seed Extract; D002392:Catechin
keywords: O-methylation; catechin; glucuronosylation; phase II metabolites; semisynthesis; structure determination; two-site validation