Covalent Binding
As one screening tool for idiosyncratic potential of drug candidates, the chemical reactivity of the compound and it's metabolites is often evaluated by quantifying their covalent binding to membranes (e.g., liver microsomes). XenoTech conducts covalent binding studies to evaluate the binding characteristics of a compound using human and non-human
hepatic protein and
hepatocytes.
A typical study design incorporates radiolabeled compounds at multiple concentrations of the compound (typically four to seven) incubated in the presence and absence of NADPH. Measurements of radioactivity and protein concentration are then used to calculate the amount of the compound bound covalently to protein. Zero-time and zero-cofactor samples are included as negative controls and a compound such as acetaminophen, known to produce covalent binding, is included as a positive control for comparative purposes.
Studies may include a comparison of protein binding between human liver microsomes and animal liver microsomes or between
in vivo and
in vitro test systems from one species.