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.
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.
Parise
Robert A
RA
Molecular Therapeutics, Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Shawaqfeh
Mohammad
M
Egorin
Merrill J
MJ
Beumer
Jan H
JH
D000284:Administration, Oral; D001562:Benzimidazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib