Gut-derived phenolic metabolites will be purified from plasma by SPE using an automated platform and in-house 96-well SPE protocol (60mg, 3mL; Phenomenex) for extraction of 100 μL tissue. All analytes have been previously optimized for extraction efficiencies of between 80-100% recoveries with CV≤10%. Extracts will be separated and quantified via liquid chromatography tandem-MS/MS involving previously published and validated methodologies. Briefly, HPLC-ESI-MS/MS analysis will be performed using a SCIEX UPLC coupled 6500 + MS/MS-QTRAP™ equipped with an electrospray ionization (ESI) Turbo-V source (blood and fecal metabolites), with samples injected onto a Kinetex PFP column and mobile phase gradient consisted of 0.1% formic acid (v/v) in water (A) and 0.1% formic acid (v/v) in acetonitrile (B), and a 24 min separation time. The targeted metabolite analysis protocol has been optimized and validated to detect greater than 200 analytes which are quantified relative to authentic commercial and synthetic standards in our library, with putative Phase II conjugates identified using fragmentation profiling involving 3-5 unique transitions. This involves scanning over 1000 transitions corresponding to sulfate, glucuronide, methyl and glycine conjugates. This SMRM methodology was previously optimized for the Rexocyn treatment and provides a significantly more sensitive method than traditional multiple reaction monitoring (MRM) scanning procedures, as it permits monitoring a greater number of transitions per unit of time, in addition to allowing unique compound-dependent parameters to be utilized for each analyte, resulting in enhanced sensitivity. Finally, metabolites will be confirmed on the basis of retention time (using authentic and synthesized standards where possible) and three or more precursor-to-product ion transitions. Seven-point matrix-matched calibration curves ranging from 0 to 10 μM will be used for the analysis of flavonoids or from 0 to 50 μM for the analysis of phenolic metabolites.