IONTOX Recommended Assays For The IND (Based On F.D.A. Guidelines) |
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Caco-2 Permeability Unidirectional - Caco-2 Cells •2 concentrations, 3 replicants, 1 time point •LC/MS/MS endpoint |
Caco-2 Permeability Bidirectional - Caco-2 Cells •2 concentrations, 3 replicants, 1 time point •LC/MS/MS endpoint |
CYP Induction - Hepatocytes •4 concentrations, 4 target CYPs, 1 time point •mRNA expression or enzyme activity/cytotoxicity endpoint |
CYP Inhibition - Microsomes/Supersomes •3 concentrations, 4 target CYPs, 4 time points •LC/MS/MS or fluorescence endpoint |
Metabolic Stability - Microsomes/Blood/Hepatocyte Model depends on molecule type •2 concentrations, 3 replicants, 2 time points •Disappearance of parent over time LC/MS/MS endpoint |
Metabolite ID - Specialized Bioanalytical dependent on metabolite •2 concentrations, 3 replicants, 6 time points •Typically LC/MS/MS combined with a secondary method endpoint |
Plasma Protein Binding - Human Plasma/Equilibrium Dialysis •2 concentrations, 3 replicants, 4 time points •LC/MS/MS endpoint |
Reaction Phenotyping - Determines which CYP enzymes contribute to metabolism: Microsomes •2 concentrations, 3 replicants, 2 time points •LC/MS/MS endpoint |
Blood Partitioning - Human Plasma/Equilibrium Dialysis •2 concentrations, 3 replicants, 4 time points •LC/MS/MS endpoint |
Transporter Interactions - Transfected Cell Models •13 transporters, 2 concentrations, 3 replicants, 1 time point •LC/MS/MS endpoint |
Cytotoxicity - (ATP, LDH, or MTT) specialized assays available on request •1 species, 6 concentrations, 3 replicants, 1 time point •Endpoint depends on assay |
Hemolysis - Fresh RBCs, Hemoglobin Release •1 species, 6 concentrations, 3 replicants, 1 time point •Hemoglobin spectrometry |