Moreover, PG has been rarely discussed as an excipient for oral delivery of biotherapeutics and detailed investigations of PG bioanalysis, metabolism, and safety considerations have been very limited to date. In order to better dissect the mechanism of PG-induced nephrotoxicity we conducted in vitro studies in human and dogs RPTECs. RPTECs have been used to evaluate the potential for renal toxicity, discovery of new biomarkers, and elucidation of mechanisms of nephrotoxicity in vitro . In order to better characterize pharmacokinetics and metabolism of PG, we developed a high sensitivity multiplexed LC-MS/MS method to quantitatively measure PG and its nine phase-I and phase-II metabolites in dog and human plasma samples, providing further understanding of PG metabolism in both species. Analytical methods such as gas and liquid chromatography have traditionally been the primary methods used to determine concentrations of PG as an antioxidant additive in foods . The use of LC-MS/MS for measurement of PG has not been commonly employed and has been limited to either in food application or utilizing PG as an internal standard of a pharmacologically active constituent in rat plasma .