Metabolite identification of ursolic acid in mouse plasma and urine after oral administration by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry

Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid widely existing in various medicinal plants, has been reported to have multifarious biological activities such as anti-inflammatory, anticancer and antioxidant activities. In this paper, we analyzed the metabolic profile of UA in mice (including plasma and urine) by using ultra-high performance liquid chromatography (UPLC) coupled with a quadrupole time-of-flight (Q/TOF) method. Principal component analysis (PCA) was applied to differentiate the control and experimental groups. Potential biomarkers were filtered by using loading plots followed by further analysis with UPLC-Q/TOF-MS data. The results showed that 3 metabolites in plasma were identified as markers, one of which was UA and the others were UA epoxides, which belonged to phase I metabolites. Additionally, 5 phase II metabolites were tentatively identified in urine through an accurate mass and characteristic fragment ions. These data suggested that the biotransformation of UA undergoes the major metabolic reactions of the phase I metabolic route of olefin oxidation and phase II metabolic routes of glycine conjugation, glutathione conjugation and glucuronidation. This is the first report of analysis and characterization of the metabolites after the oral administration of UA in mice. The proposed metabolic pathways of UA in mice is also raised for the first time. It might provide further understanding of the potential biological mechanism of UA.