Characterization of metabolites of 20(S)-protopanaxadiol in rats using ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry

• UPLC/TOF-MS procedure was for determining PPD and its metabolites in plasma, bile, urine and feces.
• Separating 23 metabolites was in less than 12 min.
• 16 metabolites of PPD were identified for the first time in rats.
• Orally administered PPD was low absorbed and extensive metabolized in rat instead of excretion.

In this study, ultra-performance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (QTOF-MS) was applied to the rapid analysis of 20(S)-protopanaxadiol (PPD) metabolites in rats after oral administration, enabling the structural characterization of 23 metabolites in plasma, bile, urine, and feces. 16 of these, including M1–M5, M9, and M11–M15, have not been previously reported. The results also indicated that demethylation, dehydration, dehydrogenation, oxidation, deoxidation, and glucuronidation were the major metabolic reactions of PPD in vivo. This study provides important information about the metabolism of PPD which will be helpful for fully understanding its mechanism of action. Furthermore, structural modification of PPD in vivo may aid in obtaining new chemical derivatives for pharmacological screening.