1. The most commonly obtained pharmacological assay for concentration of polyphenols or their metabolites is blood plasma analysis, rather than interstitial fluid or intracellular fluid. 2. A polyphenol's plasma concentration profile alone provides no data on tissue distribution or biotransformation. 3. It is very difficult to sample intracellular fluid for drug/metabolite concentration profiling to the exclusion of extracellular and serum fluid. 4. Even radiolabeled assaying of all possible elimination routes fails to provide a complete accounting of polyphenol dosage intake. 5. Plasma samples of polyphenols are more frequently obtained from healthy individuals, rather than those suffering from a particular pathology. Therefore if any particular pharmaceutical candidate's PK profile achieves significant distribution in organs other than those associated with either the GI tract or renal tract, it would be unascertainable from serum analysis alone. Further, if any particular pathology has an effect on a compound's tissue distribution (whether by causing sequestering in sanctuary sites, or adduct formation with the target in tissue both of which represent an increase in the volume of distribution), then plasma analysis alone remains poorly positioned to provide the relevant readout. Rather, tissue analysis in sacrificed animal models, or comprehensive radiolabeled elimination quantitation in humans, would be required. ) demonstrated such a radiolabeled analysis . Notably, they found that carbon dioxide was a major metabolite of quercetin in humans, suggesting a rarer elimination pathway than typically encountered by pharmacological analysis. Even with this exotic elimination route taken into account, the full dose of quercetin was not always accounted for. One can speculate that sequestration of quercetin products in tissue compartments was maintained past the 72-hr study period.