Metabolic stability





Metabolic stability of drugs plays an important role in their bioavailability, and affects the pharmacokinetic properties. The decrease of stability results in an increase in drugs excretion from the organism, which in consequence leads to a significant reduction in their bioavailability. Metabolic stability studies of new drugs help to determine their pharmacokinetic parameters (half-life, clearance, absorption). This kind of studies allows scientists to specify the size of the dose and frequency of administration.

BioCentrum provides two highly efficient methods for metabolic stability studies. The main aim of both methods is to establish metabolic stability of testes compounds. The one uses liver microsomes, which contain the majority of enzymes responsible for xenobiotics metabolism. The second method uses S9 fraction, which is the supernatant obtained from differential centrifugation at 9000g of strained liver homogenate. This fraction contains both the cellular cytosol and the ER membranes with their respective metabolic enzymes.
In both methods tested compounds are preincubated with microsomes or S9 fraction for 10 min at 37 °C. The reaction is initiated by addition of 1mM UDPGA or 1mM NADPH and incubated for 15 to 30 min at  37 °C. Thanks to the high-performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (LC-MS/MS), both methods allow to detect tested compounds after incubation with microsomes or S9 fraction.