Unforeseen matrix interferences, that were not observed in pre-dose or placebo samples, were observed in plasma samples upon administration of PG. The quantitative measurement of PG and 4OMGA from pharmacokinetic samples was confounded by matrix interferences. To address the method limitations due to interference, extensive chromatographic optimizations such as optimizing columns, gradients, mobile phases, flow rate and column temperature were evaluated to resolve the analyte peak and to separate the analyte from matrix interference (Supplemental Figure ). An impact of hemolysis on PG and GA quantification was also observed even at such low levels as 0.05 %. However, their respective internal standards also showed similar response as the analytes. As a result, the impact of hemolysis on propyl gallate quantification can be controlled with a stable labeled internal standard (Supplemental Figure ).