Discovery bioanalysis and in vivo pharmacology as an integrated process: a case study in oncology drug discovery

Abstract

Background: A bioanalytical team dedicated to in vivo pharmacology was set up to accelerate the selection and characterization of compounds to be evaluated in animal models in oncology. Results: A DBS-based serial microsampling procedure was optimized from sample collection to extraction to obtain a generic procedure. UHPLC–high-resolution mass spectrometer configuration allowed for fast quantitative and qualitative analysis. Using an optimized lead compound, we show how bioanalysis supported in vivo pharmacology by generating blood and tumor exposure, drug monitoring and PK/PD data. Conclusion: This process provided unique opportunities for the characterization of drug properties, selection and assessment of compounds in animal models and to support and expedite proof-of-concept studies in oncology.