Identification of metabolites of meisoindigo from interspecies microsomes and in vivo biological fluids in rats by liquid chromatography tandem mass spectrometry

Abstract

Meisoindigo has been a routine therapeutic agent for CML in China. However, information relevant to its metabolism is limited. In this thesis, in vitro metabolism studies were firstly carried out in rat, pig and human liver microsomes of different genders by LC-MS/MS. The in vitro metabolic pathways of meisoindigo in three species were proposed. Statistical analysis showed there were no significant differences in the metabolic stability profiles of meisoindigo among three species, and gender effect was negligible. Secondly, in vitro extrahepatic metabolism of meisoindigo in rat kidney microsomes was qualitatively and quantitatively investigated by LC-MS/MS. Thirdly, in vivo circulatory metabolites of meisoindigo in male rat plasma, excretory metabolites in male rat urine and feces were identified by LC-MS/MS. The phase I metabolic pathways showed a significant in vitro-in vivo correlation in rat. This study shed new light in the metabolic profiles of meisoindigo in rat, pig and human.