@article{APS7842,
author = {Lu SUN and Shu-qiu ZHANG and Da-fang ZHONG},
title = {In vitro identification of metabolites of verapamil in rat liver microsomes},
journal = {Acta Pharmacologica Sinica},
volume = {25},
number = {1},
year = {2016},
keywords = {},
abstract = {AIM:
To investigate the metabolism of verapamil at low concentrations in rat liver microsomes.
METHODS:
Liver microsomes of Wistar rats were prepared using ultracentrifuge method. The in vitro metabolism of verapamil was studied with the rat liver microsomal incubation at concentration of 1.0 micromol/L and 5.0 micromol/L. The metabolites were separated and assayed by liquid chromatography-ion trap mass spectrometry (LC/MSn), and further identified by comparison of their mass spectra and chromatographic behaviors with reference substances.
RESULTS:
Eight metabolites, including two novel metabolites (M4 and M8), were found in rat liver microsomal incubates. They were identified as O-demethyl-verapamil isomers (M1-M4), N-dealkylated derivatives of verapamil (M5-M7), and N,O-didemethyl-verapamil (M8).
CONCLUSION:
O-Demethylation and N-dealkylation were the main metabolic pathways of verapamil at low concentrations in rat liver microsomes, and the relative proportion of them in verapamil metabolism changed with different substrate concentrations.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7842}
}