Oral delivery, as a non-invasive drug administration route for peptides and biologics, has been of growing interest for the development of chronically administered medications since it can significantly improve the patient experience. Novel design of formulation is one of the means to enhance drug properties such as permeability and solubility. Propyl gallate, an excipient commonly used in food and cosmetics to avoid oxidation, has been recently found to enhance the bioavailability of a GLP-1 agonist, MEDI7219, when formulated as an enteric coated tablet. As a novel excipient (ie, used at higher levels than in approved oral medications), pharmacokinetic and toxicokinetic measurements of PG and its metabolites are important to establish exposure-based safety margins. Preclinical toxicology studies in dogs have revealed that PG delivered via entericcoated tablets induced renal toxicity. In vitro assessments using RPTEC identified possible sensitivity difference between dogs and humans, providing further understanding of potential translatability of PG-induced dog renal toxicity to humans. Mechanistic investigations by cell- based assays with RPTEC suggested GSH-mediated detoxification was less effective in dog cells than in human cells. A highly multiplexed, robust and sensitive LC-MS/MS-based method was developed for the quantification of PG and its nine phase I&II metabolites in both dog and human plasma. The methods were evaluated and validated comprehensively to support evaluation of PG safety and pharmacokinetics. Species differences in PG drug metabolism at molecular level were further investigated using the LC-MS/MS assay. Some exposure differences in phase-II metabolites of PG were observed in circulation between humans and dogs as was observed a difference in overall exposure, assuming allometric scaling.