Model | In-vitro model for metabolic stability |
Test System | Human Liver Microsomes, S9, Hepatocytes |
Species | Rodent & Non-rodent (as per request) |
Quantitation method | HPLC-UV or LC/MS/MS |
Positive control | Suitable substrate |
Deliverables | Parent compound loss, in-vitro half life |
Model | In-vitro model for matrix stability |
Test System | Plasma, serum, blood, CSF, Tissue, aqueous buffers |
Quantitation method | HPLC-UV or LC/MS/MS |
Deliverables | Parent compound loss, in-vitro half life |
Model | In-vitro model for cytochrome P450 Inhibition |
Test System | Human Liver Microsomes or recombinant enzymes |
Quantitation method | HPLC-UV or LC/MS/MS or Fluorescence reader |
Positive control | Suitable substrate |
End Point | Metabolite formation |
Deliverables | Percent inhibition, IC50 determination |
Model | In-vitro model for drug-drug or herb-drug interaction |
Test System | Human Liver Microsomes or recombinant enzymes |
Method | Co-incubation of herb-drug or drug-drug with CYP enzymes |
Quantitation method | HPLC-UV or LC/MS/MS or Fluorescence reader |
End Point | Metabolite formation |
Deliverables | Percent inhibition, IC50 determination, Drug interaction potential |
Model | In-vitro model for CYP450 Reaction Phenotyping |
Test System | Human Liver Microsomes or recombinant enzymes |
Quantitation method | HPLC-UV or LC/MS/MS or Fluorescence reader |
Method | Selective inhibitor for CYP450 – to determine cytochrome P450 involved in metabolism |
End Point | Metabolite formation |
Model | In-vitro model for CYP450 Induction |
Test System | Human Hepatocytes, Cell line (LS180) |
Quantitation method | LC/MS/MS & RT-PCR |
Positive Control | Suitable Substrate |
Method | Determination of enzyme activity and m-RNA levels |
End Point | Metabolite formation |
Model | In-vitro model for Plasma Protein Binding |
Test System | Plasma, serum, whole blood, purified proteins (Albumin, AGP) |
Species | Rodent and non-rodent (as per request) |
Quantitation method | LC/MS/MS or HPLC-UV |
Method | Rapid equilibrium dialysis (RED), Ultrafiltration |
Deliverables | Percent protein binding |
Model | In-vitro model for metabolite ID/profiling |
Test System | Human Liver Microsomes, S9, Hepatocytes |
Species | Rodent and non-rodent (as per request) |
Quantitation method | LC/MS/MS or HPLC-UV |
Deliverables | Metabolite identification/profiling based of m/z found, mass difference from parent compound, possible addition or deletion |
Model | In-vitro model for determination of Blood to plasma ratio |
Test System | Whole Blood & Plasma |
Species | Rodent and non-rodent (as per request) |
Quantitation method | LC/MS/MS or HPLC-UV |
Deliverables | Blood to plasma ratio |
Model | In-vitro model for permeability & Efflux (Caco-2 & MDCK) |
Test System | Caco-2, MDCK cell lines |
Method | Unidirectional or bidirectional |
Quantitation method | LC/MS/MS or HPLC-UV |
Deliverables | Permeability Coefficient, Efflux ratio |
Model | In-vitro model for Dermal Absorption/penetration |
Test System | Rat Skin, Human skin, artificial membranes |
Quantitation method | LC/MS/MS or HPLC-UV |
Deliverables | Permeability Coefficient (Kp), Flux |