Pharmacokinetic, Bioavailability, and Excretion Study of Cistanoside A Following Intragastric and Intravenous...

Cistanoside A (Cis A) has received more attention because of its potential in the treatment of osteoporosis. However, its in vivo process remains unknown. In this study, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of cistanoside A in rat plasma, urine, and feces. After prepared by protein precipitation, cistanoside A and IS were separated on a Waters BEH C18 column with MS detection operated in positive multiple reaction monitoring mode. The method was fully validated and applied to the pharmacokinetic and excretion studies of cistanoside A in rats after intravenous (5 mg/kg) and oral (10, 20, and 40 mg/kg) administration. After intravenous administration, cistanoside A showed moderate clearance (0.52 ± 0.04 L*h/kg), low volume of distribution, and short terminal half-life (0.43 ± 0.03 h). After oral administration at doses of 10, 20, and 40 mg/kg, the system exposure increased lower than the increase of dose, and the oral bioavailabilities were 0.39%, 0.38%, and 0.23%, respectively. After oral administration, the average cumulative excretion rate was 0.03% in urine and 1.62% in feces at 24 h. In summary, this study defined the pharmacokinetic and excretion characteristics of cistanoside A in rats, which could provide useful information for its further development.