In vitro cross-species metabolism
The incubation of drug candidates with liver microsomes and/or hepatocyte suspensions from human and animal species aims to identify and quantify hepatic metabolites, enabling or confirming the selection of species for toxicological studies. Metabolite structure elucidation is supported by orthogonal parameters such as accurate mass and multi-stage mass (MSn) experiments. Our cross-species metabolism assay typically uses radiolabelled test compounds, with parent drugs and metabolites quantified by radioactive measurement via off-line scintillation counting. Using unlabelled test compounds is feasible but allows only semi-quantitative assessments based on mass-spectrometric responses. The assay can be supplemented by determining covalent binding of radiolabelled test compounds to hepatocyte or microsomal proteins, providing indications of reactive metabolite formation and assessing potential risks for idiosyncratic toxicity.
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