Investigation of metabolic stability and metabolic enzyme phaenotypes of anti-tumor compound HK-7 in different species of liver microsomes by UPLC-MS/MS
XIA Yuan-yuan
YANG Ju-qin
ZHU Yi-ting
CHEN Ying-jie
TANG Ming-hai
WAN Li
Abstract：Objective:To investigate the metabolic stability of HK-7 in liver microsomes of human,SD rats,Kunming mice,Rhesus monkeys and Beagle dogs,and identify the main enzymes involved in HK-7 metabolism in human liver microsomes.Methods:After being incubated with different species of liver microsomes,HK-7 was quantified by UPLC-MS/MS method to evaluate its stability and metabolic kinetic parameters in vitro.The CYP450 phenotype of HK-7 was identified by specific inhibitors of isoforms in human microsomal incubation system.Results:The in vitro half-lives (t1/2) of HK-7 in liver microsomes of human,SD rats,Kunming mice,Rhesus monkeys and Beagle dogs were 44.91,83.42,72.70,48.93,and 66.21 min respectively.Their intrinsic clearance rates (CLint) were0.031,0.016,0.019,0.028,and0.021 mL·min-1·mg-1,respectively.CYP2C9,CYP2E1,and CYP3A4 were found to be the major CYP isoforms involved in HK-7 metabolism.Conclusion:There is significant difference in the metabolic rate of HK-7 between different species.The metabolism of HK-7 in human liver microsomes may be CYP2C9,CYP2E1 and CYP3A4,and CYP2E1 has the greatest contribution to its metabolism.
Keywords：HK-7metabolicstabilityliver microsomesmetabolic phenotyping
Publication Date：2018-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 178-183 )