Structural characterization of minor metabolites and pharmacokinetics of ganoderic acid C2 in rat plasma by HPLC coupled with electrospray ionization tandem mass spectrometry

The metabolites and pharmacokinetics of ganoderic acid C2 (GAC2), a bioactive triterpenoid in Ganoderma lucidum in rat plasma were investigated by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI-MS/MS). Totally, ten minor phase I metabolites of GAC2 were characterized after oral administration of GAC2, on the basis of their mass fragmentation pathways or direct comparison with authentic compounds by high-performance liquid chromatography coupled with diode array detection and electrospray ion trap tandem mass spectrometry (HPLC–DAD–ESI-MSn), and liquid chromatography coupled with electrospray ionization hybrid ion trap and time-of-flight mass spectrometry (LC–ESI-IT-TOF/MS) methods. Moreover, a rapid and specific method for quantification of GAC2 in rat plasma after oral administration was developed by using a liquid–liquid extraction procedure and HPLC–ESI-MS/MS analysis. It is the first time to report the metabolites and pharmacokinetics of GAC2.

Graphical abstractProposed metabolic pathways of ganoderic acid C2 (M0) in rats.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Ten minor phase I metabolites were characterized. ► A rapid quantification method was developed by LC–MS/MS. ► The metabolites and pharmacokinetic of GAC2 were reported firstly.