Metabolic stability 

Accurate prediction of hepatic intrinsic clearance for drug discovery  

Hepatic intrinsic clearance reflects the inherent ability of hepatocytes or subcellular systems (e.g., microsomes, S9 fractions) to eliminate unbound drugs, governed by metabolising enzyme activity. Accurate scaling of in vitro clearance is crucial for predicting drug exposure, dose, half-life and bioavailability in humans and preclinical species.  
 
Our metabolic stability assays use fully automated robotic systems, enabling high throughput and quick turnaround times. The assays can utilise hepatocytes or liver microsomes from humans and various animal species, including mouse, rat, monkey, mini pig and dog. Based on your requirements, pharmacokinetic parameters such as compound half-life (t1/2) and in vitro intrinsic clearance (CLint) can be reported. Additionally, intrinsic clearance in human hepatocytes can predict human hepatic blood clearance using the well-stirred liver model and the maximum achievable bioavailability (% Fmax). We also offer specialised 4-hour incubation and CYP3A4 fraction metabolised assays in human hepatocytes upon request.  

Our assay is conducted with unlabelled small molecule compounds using cryopreserved hepatocytes in suspension. Quantification is performed using liquid chromatography-tandem mass spectrometry or high-resolution mass spectrometry, with the option for metabolite identification.