Pharmacokinetic, bioavailability, and metabolism studies of lusianthridin, a dihydrophenanthrene compound, in rats by liquid chromatography/electrospray ionization tandem mass spectrometry

Lusianthridin was reported to possess many biological properties such as anti-oxidant and anti-cancer activities. However, its metabolic profiles and pharmacokinetics in vivo remain unknown. This study was carried out to investigate the metabolic profiles and pharmacokinetics of lusianthridin in rats. The metabolic profiles were obtained by an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). A total of eighteen metabolites involved three phase I metabolites and fifteen phase II metabolites were detected and identified. The major metabolic pathways of lusianthridin were demethylation, oxidation, sulfation, glucuronidation and glutathione conjugation. In addition, a simple and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established for determination of lusianthridin in rat plasma. After extracted by protein precipitation, lusianthridin was quantitated in positive ion mode. The method was linear over the range of 0.5-500 ng/mL (r ≥ 0.995) with the LLOQ of 0.5 ng/mL. The intra- and inter- precision and accuracy, extraction recovery, matrix effect and stability were within the acceptable limits. The validated method was applied to the pre-clinical pharmacokinetic study of lusianthridin in rats. After oral administration, lusianthridin was quickly absorbed into plasma and reached the max concentration of 236.22 ng/mL at 22.00 min. The elimination half life of lusianthridin from plasma was approximately 83.05-104.47 min and the oral absolute bioavailability was calculated as 30.93 %.