Metabolic Stability

Overview

Metabolic stability influences both oral bioavailability and plasma half-life of a compound, which in turn, affect its efficacy. Sekisui XenoTech evaluates the metabolic stability of drug candidates in a variety of in vitro test systems (S9, microsomes and hepatocytes). Human liver microsomes and hepatocytes have been well established as the test system of choice to study cytochrome P450 dependent and conjugation of drugs, respectively.


Results

Our contract service assesses the stability of the compound relating to biotransformation by measuring the disappearance of parent compound in the selected in vitro test system.

  • LC/MS method development for analysis of test article
  • Incubations in suitable test system (S9, microsomes, hepatocytes, recombinant CYP enzymes) with appropriate cofactors and measured at multiple time-points in triplicate, with additional replicates for critical samples
  • Comparisons of time and cofactor blanks
  • Incubations of marker substrates (e.g., 7-ethoxycoumarin) as positive controls to check for metabolic competency of the test system
  • Data summary


Discovery Plus™ Metabolic Stability Screen

Our Medium Throughput Metabolic Stability Screen is designed to screen the effects of up to 16 test articles on specific metabolism with various in vitro test systems (S9, microsomes, hepatocytes).
  • Generic LC/MS method, generic IS will be used for sample analysis
  • Screens are performed at four optional time points (short-, medium-, long-time course options, the longest time point being 120 minutes)
  • Number of replicates selected by client
  • Positive controls included
  • Tabular data summary

View our Discovery Plus™ Metabolic Stability Screen Poster
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<< Drug Metabolism
Metabolite Characterization
Plasma Protein & Covalent Binding
CYP and UGT Reaction Phenotyping
Species Comparison
Non-CYP Metabolism
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