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.

Keywords::

• biomarker
• DBS
• drug monitoring
• HRMS
• mice
• PK/PD
• serial microsampling

Supplementary Data

Financial & competing interests disclosure

All authors were employees of Laboratoires Pierre Fabre at the time of the work described. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank Valérie Cartron who contributed greatly to setting up an efficient workflow between in vivo pharmacologists and the bioanalysis team, and Nathalie Borotra and Grégory Déïdé who performed the bioanalytical analyses. The authors are also grateful to Deborah Carayol for proofreading the manuscript.