ABSTRACT
To investigate the metabolic stability and parameters in vitro of lanceolatin B in liver microsomes of rats, human, Beagle dogs, and monkeys, and to identify the phaenotypes of CYP enzymes of lanceolatin B by using the liver microsome incubation system in vitro. After incubated with different species of liver microsomes, lanceolatin B was quantified by UPLC-MS/MS method to evaluate its metabolic stability and metabolic kinetic parameters in vitro. Lanceolatin B was incubated with specific inhibitors of CYP450 isoforms (CYP2E1, 2C19, 1A2, 2D6, 2C9, 3A4, and 2A1) to determine the phaenotypes of metabolic enzymes. The results showed that lanceolatin B was metabolized in the liver microsomes of rats and monkeys but not in the human and Beagle dogs. Their in vitro half-life T1/2 and intrinsic clearance rate CLint in rat and monkey liver microsomes were 11.57,8.07 min, and 0.12,0.17 mL•min⁻¹•mg⁻¹ without significant difference. The results of metabolic phenotyping indicated that CYP1A2 was mainly involved in the metabolism of lanceolatin B. There existed a difference in the metabolism of lanceolatin B in different types of liver microsomes. Several of CYP450 isoforms metabolized lanceolatin B together in liver microsomes of rats, in which CYP1A2 was the major enzyme mainly responsible for the metabolism of lanceolatin B.