Liquid chromatography-mass spectrometric assay for the quantitation in human plasma of ABT-888, an orally available, small molecule inhibitor of poly(ADP-ribose) polymerase

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Sep 1;872(1-2):141-7. doi: 10.1016/j.jchromb.2008.07.032. Epub 2008 Jul 31.

Abstract

ABT-888, a poly(ADP-ribose) polymerase (PARP) -inhibitor in clinical trials, potentiates DNA-damaging agents. We developed and validated, according to FDA guidelines, an LC-MS assay for sensitive, accurate and precise quantitation of ABT-888 and its metabolite M8 in 0.2 mL human plasma. After ethyl acetate extraction, separation is achieved with a hydro-Synergi column and a 0.1% formic acid in acetonitrile/water-gradient. Detection uses electrospray, positive-mode ionization mass spectrometry. Between 10 (LOQ) and 1000 ng/mL, accuracy was 95.5-98.5% for ABT-888 and 91.4-100.9% for M8, and precision was 0.1-4.9% for ABT-888 and 0-13.7% for M8. The assay is being applied to samples generated in several clinical trials.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / blood*
  • Benzimidazoles / pharmacokinetics
  • Calibration
  • Chromatography, Liquid / methods*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / blood*
  • Enzyme Inhibitors / pharmacokinetics
  • Humans
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Reference Standards
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization / methods*

Substances

  • Benzimidazoles
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • veliparib