Pharmacokinetic, Bioavailability, and Excretion Study of Hypaphorine Following Intragastric and Intravenous Administration in Rats Using Ultra‐High Performance Liquid Chromatography Tandem Mass Spectrometry

Hypaphorine is an indole alkaloid from Erythrina velutina, which exerts excellent anti-inflammatory and antioxidant properties. In this study, a simple liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of hypaphorine in rat plasma, urine, and feces. After acetonitrile-mediated protein precipitation, hypaphorine, and IS were separated on a 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 hypaphorine in rats after intravenous (1 mg/kg) and oral (5, 10, and 20 mg/kg) administration. After administration, hypaphorine showed low clearance (0.31 ± 0.06 L*h/kg), moderate volume of distribution, and moderate terminal half-life (5.61-7.33 h). After oral administration at doses of 5, 10, and 20 mg/kg, the system exposure increased slightly lower than the increase of dose, and the oral bioavailability values were 29.19%, 25.72%, and 20.06%, respectively. After intravenous administration, the cumulative excretion rate of hypaphorine was 25.80% in urine and 0.60% in feces. After oral administration, the cumulative excretion rate of hypaphorine was 8.22% in urine and 16.60% in feces at 48 h. In summary, this study defined the pharmacokinetic and excretion characteristics of hypaphorine in rats, which could provide useful information for its further development.