Identification of metabolites produced in rat and human hepatocytes

Reaction mixtures contained 250,000 hepatocytes per incubation and drug at 10 μM concentration. Metabolite analysis was performed with a Waters LC/MS instrument, as described under Materials and Methods. Tentative metabolite identification based on MS/MS fragmentation, m/z, retention time, and species identified are shown.

DrugMetaboliteTentative Metabolite Identificationm/zRT (min)Species
AP + O – 2 H4572.71RH, HH
BP + glucuronide6192.49HH
CP + O + sulfate5392.29RH, HH
DP + O + glucuronide6352.04HH
GlibenclamideParent4942.76RH, HH
AP + O5102.57RH, HH
BP + O5102.36RH, HH
CP + O5102.31RH, HH
DP + O5102.28RH, HH
EP + O5102.24RH, HH
FN-dealkylation4122.18RH, HH
AP + O4562.89RH, HH
BP + sulfate5202.47RH, HH
CP + glucuronide6162.24RH, HH
DP + O + sulfate5362.14RH
EP + O + sulfate5362.35RH, HH
FP + O + 2H + sulfate5382.01RH, HH
GP + O + O4722.36RH, HH
RosiglitazoneParent3582.69RH, HH
AP + O3742.27RH, HH
BN-desmethyl3442.36RH, HH
CN-desmethyl + O3602.00RH, HH
DP + O + glucuronide5501.92RH, HH
EP + O3741.97RH, HH
  • RT, retention time; RH, rat hepatocyte; HH, human hepatocyte.