Characterization of picroside II metabolites in rats by ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

Abstract

Picroside II, a bioactive compound isolated from Picrorhiza scrophulariiflora Pennell, has been reported to have hepatoprotective, neuroprotective, and antioxidant effects. However, the detailed in vivo biotransformation of this compound has been rarely reported. This study aimed to investigate the metabolic profiles of picroside II in rats by using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Metabolite structures were elucidated based on accurate mass measurements of deprotonated molecules and their fragmentation patterns. Thirteen metabolites were structurally identified, and the detailed metabolic pathways were proposed. The findings revealed that after oral administration, picroside II mainly undergoes four metabolic pathways. In the first pathway, picroside II is deglycosylated to generate aglycone, which is isomerized to a dialdehyde-type intermediate. A series of metabolic reactions, including glucuronidation, subsequently occurs. In the second pathway, picroside II is subjected to ester bond hydrolysis to form vanillic acid, which is further subjected to sulfate conjugation, glycine conjugation, glucuronidation, and demethylation. In the third pathway, picroside II is directly conjugated with glucuronic acid to yield a predominant metabolite (M01) in plasma. In the fourth pathway, picroside II is directly conjugated with sulfate. These findings provide insights into the in vivo disposition of picroside II and are useful to understand the mechanism of effectiveness and toxicity of this compound as well as P. scrophulariiflora-related preparations.