Automating Metabolic Stability Assays and Analyses Using a Robotic Autosampler and LC-MS/MS Platform
The liver is the principal organ involved in mammalian metabolism of xenobiotics including drug compounds. Microsomes are isolated through differential centrifugation of liver tissue homogenate and are principally derived from the membranes of the endoplasmic reticulum. These microsomes provide an enriched source of membrane bound drug metabolising enzymes including the cytochrome P450 (CYP) superfamily and uridine glucuronosyl transferase (UGT) enzymes. To study and assess the metabolism of chemical drug compounds, DMPK laboratories can perform in vitro studies using liver microsomes.
As a result of this study, we were able to show that an in vitro metabolic stability assay and subsequent sample preparation method can be successfully automated using the GERSTEL MPS robotic sampler for a variety of model drug compounds in microsomes. Using this method, analytes can be rapidly and reproducibly isolated from microsome samples using an automated procedure coupled to LC-MS/MS analysis using the Agilent Ultivo Triple Quadrupole Mass Spectrometer.
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