Single Time Point Microsomal Stability Pre-Screen

Background: At early drug discovery stages it is critical to rapidly evaluate the metabolic stability of many new chemical entities. Single time point microsomal stability pre-screen assay, focused on stability ranking of large compound sets, allows increasing throughput and reducing costs. Moderate incubation time used in this assay (e.g. 15 min for mouse liver microsomes) provides valid metabolic stability evaluations for both unstable and stable compounds, which are in good agreement with those derived from the standard multi time point experiments.

Service Details: Single time point microsomal stability pre-screen is a 96-well plate automated assay performed on sets starting from 30 compounds. Test compounds are incubated with microsomes under the standard hepatic microsomal stability assay conditions. The parent compound loss is evaluated by LC-MS/MS measurements (API5000 detector, AB Sciex). This service also includes incubation of two control drugs and a control without co-factors.

Deliverable: Data include parent compound percent remaining. Full study report is provided.

Sample Submission: A minimal accurately weighable quantity of dry compound (~1 mg or 2 µmol) or 50 µL of 10-20 mM stock DMSO solution is required for this assay. For multiple assays, lesser amount of compound per assay may be sufficient, which should be discussed for each particular project. We do not need to know structures of the molecules for ADME testing. However, we ask our customers to provide brutto formulas for all studies involving MS detection.