Metabolism of isorhynchophylline in rats detected by LC-MS

Abstract

Purpose. This paper investigates the metabolic fate of isorhynchophylline (ISOR) as a main bioactive oxindole alkaloid in the traditional Chinese medicine, Uncaria species. Methods. After oral administration of ISOR to rats, plasma, bile, urine and feces were analyzed by LC-MS. Hydroxylation of ISOR and successive glucuronidation proceeded in vitro by incubation with rat liver microsomes. Results. ISOR was identified in plasma, bile, urine and feces. 11-Hydroxyisorhynchophylline 11-O-β-D-glucuronide (MI1) and 10-hydroxyisorhynchophylline 10-O-β-D-glucuronide (MI2) were found in bile, and free 11-hydroxyisorhynchophylline (MI3) and 10-hydroxyisorhynchophylline (MI4) were found in urine and feces. Within 24 h, 71.6% of ISOR was found in the feces and 13.8% into the urine of rats after oral administration of 37.5 mg/kg. Monitoring by LC-MS showed that 8.5% of ISOR was metabolized to MI3 and MI4 in a ratio of ca. 1:1. Specific inhibition of CYP isozymes indicated that CYP2D, CYP1A1/2 and CYP2C participate in ISOR hydroxylation. Conclusions. ISOR was found in the circulatory system after oral administration. Cytochrome P450 in rat liver microsomes played a key role in ISOR hydroxylation.