Automating Metabolic Stability Assays and Analyses

The in vitro metabolic stability of potential drug candidates is routinely examined at an early stage of drug discovery. Metabolic stability is a simple, well-established screening technique used to predict the in vivo hepatic clearance of a drug based on due to metabolism. With the ever-increasing chemical libraries, today’s drug metabolism and pharmacokinetic (DMPK) laboratories are constantly being asked to increase the number of molecules that can be assayed to decrease the time needed to identify lead drug candidates.

Automating the entire metabolic stability assay and subsequent LC-MS/MS analysis provides the high throughput necessary for DMPK laboratories. The GERSTEL MPS robotic autosampler performs syringe transfer of all liquids involved in the metabolic stability procedure including temperature-controlled incubation of the samples for defined time periods. Additional sample preparation steps are performed as needed. The resulting extracts from the automated method were introduced into an Agilent Ultivo LC/MS/MS instrument.