title: In vitro identification of metabolites of verapamil in rat liver microsomes.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.forename: Shu-Qiu
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D002121:Calcium Channel Blockers; D014700:Verapamil