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Acta Pharmacol Sin. 2004 Jan;25(1):121-8.

In vitro identification of metabolites of verapamil in rat liver microsomes.

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1
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.

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.

PMID:
14704133
[Indexed for MEDLINE]
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