First pass metabolism is an important factor that affects the oral bioavailability of drugs. Metabolism affects a drug’s clearance and duration of action (half-life); drugs with high clearance often have a short half-life. The metabolism of the drug in the body and whether it forms metabolites are also important parameters in assessing the bioavailability, toxicity, and dosing potential for drug-drug interaction of a compound.
Estimates of in vivo metabolic clearance can be determined from in vitro metabolism kinetic data. Metabolic stability assays are typically performed to estimate a drug candidate’s metabolic half-life, or derive its intrinsic clearance. The analytical approach outlined in this note incorporates specificity, increased sensitivity, and higher throughput via decreased method development and analysis runtime, compared to traditional methods. The use of UPLC®/MS/MS and specialized software (ProfileLynx™ and QuanOptimize™ Application Managers) allowed for the automation of the analysis with faster time to results.
Using the ProfileLynx and QuanOptimize applications allowed for: