iHUMITE®: comprehensive human drug metabolite profiling

FDA/ICH MIST require that all ">10%" human plasma metabolites are characterised as early as possible with coverage checked in tox species. Traditional in vitro (incomplete biotransformation) and/or "cold compound First-in-Man" studies followed by LC-MS (operator dependent profiling) risk missing major human metabolites. The low predictive value of early human metabolite ID results in serious risk of exceeding timelines due to new metabolite findings in phase 3 14C studies. For timely results with your compounds a cost effective and efficient workflow for the identification of human metabolites in plasma has been developed: iHumite.

iHumite workflow

• Metabolite prediction
  Potential metabolites are predicted using biotransformation rules derived from a large set of metabolic reactions (ChemMedChem, 2008, 3, 821). This algoritm predicted 85 % of all major human metabolites correctly (ASMS 2012).
• Accurate LC-MS
  Targeted LC-MS analysis is used to confirm predicted metabolites (85% hit rate). As a result of this iHumite workflow strategy, less time has to be spent on the remaining 15% in pooled plasma of dosed vs. placebo dosed subjects.
• Data Processing
  MS vendor independent software (MsMetrix MsXelerator) reads the predicted metabolite set and reports the combined results of both the targeted (predicted) and nontargeted (unexpected) metabolite searches.