Species differences in caffeine metabolism in liver microsomes of rats and mice

Abstract

Caffeine and its metabolic products play an important role in clinical applications. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF MS/MS) method was applied to systemically study the caffeine metabolism in liver microsomes of rats and mice, and comprehensively evaluate caffeine metabolites in vitro and metabolism differences between species. The caffeine metabolites and metabolism differences between species in liver microsomes of rats and mice were analyzed by UPLC-Q-TOF-MS/MS high resolution mass spectrometry system and metabolitepolite software. The results showed that in addition to the demethylated and oxidized products in previous analysis, methylated, double oxidized, dehydrated and decarbonylated metabolites were also found in caffeine metabolism in liver microsomes of rats and mice, with significant difference in metabolism in vitro between rats and mice. The demethylated metabolite M2(C7H8N4O2) and decarbonylated metabolite M6(C7H10N4) in metabolism in vitro of mice were not found in rats, and the in vitro metabolite M7(C8H12N4O5) in rats were not found in mice. There was significant species difference in caffeine metabolism in vitro between rats and mice, providing important reference value for the further metabolism study and safety evaluation of caffeine.