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Development of a sensitive LC-MS/MS assay to support human microdose study for an oral agonist of the GLP-1 receptor.

Eugene P KadarHeather EngAmit S KalgutkarChristopher L HollimanGregory S Steeno
Published in: Bioanalysis (2024)
Aim: The purpose of this work was to determine the feasibility of supporting a clinical microdose study for PF-06882961 (danuglipron), an oral small molecule agonist of the GLP-1 receptor, by LC-MS/MS. Methodology: Statistical instrument parameter optimization using response surface methodology was employed to develop a LC-MS/MS method for the analyte, PF-06882961. Results: An LC-MS/MS method was developed and validated to support a proof of concept microdose pharmacokinetics preclinical study in monkeys, administered PF-06882961 (0.005 mg total, average dose = 0.0007 mg/kg) via intravenous bolus injection. Conclusion: The present study demonstrated the feasibility of analyzing human microdose plasma samples for PF-06882961 by LC-MS/MS, instead of accelerator mass spectrometry, thereby reducing cost and eliminating synthesis and exposure to 14 C labeled material.
Keyphrases
  • small molecule
  • mass spectrometry
  • stem cells
  • low dose
  • computed tomography
  • high dose
  • liquid chromatography
  • bone marrow
  • cell therapy
  • binding protein
  • tandem mass spectrometry