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


CONCLUSIONS
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.
Laboratoires Pierre Fabre, Institut de Recherche Pierre Fabre, 3, Avenue Hubert Curien, BP 13562, 31035 Toulouse, France.
Antonio
A
Grondin
Laboratoires Pierre Fabre, Institut de Recherche Pierre Fabre, 3, Avenue Hubert Curien, BP 13562, 31035 Toulouse, France.
Arnaud
A
Pillon
Laboratoires Pierre Fabre, Institut de Recherche Pierre Fabre, 3, Avenue Hubert Curien, BP 13562, 31035 Toulouse, France.
Isabelle
I
Vandenberghe
Laboratoires Pierre Fabre, Institut de Recherche Pierre Fabre, 3, Avenue Hubert Curien, BP 13562, 31035 Toulouse, France.
Nicolas
N
Guilbaud
Laboratoires Pierre Fabre, Institut de Recherche Pierre Fabre, 3, Avenue Hubert Curien, BP 13562, 31035 Toulouse, France.
Anna
A
Kruczynski
Laboratoires Pierre Fabre, Institut de Recherche Pierre Fabre, 3, Avenue Hubert Curien, BP 13562, 31035 Toulouse, France.|iTeos Therapeutics, Rue Auguste Piccard 48, 6041 Gosselies, Belgium.
Bruno
B
Gomes
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D059788:Dried Blood Spot Testing / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice
D000970:Antineoplastic Agents
DBS; HRMS; PK/PD; biomarker; drug monitoring; mice; serial microsampling