Simultaneous determination of ABT-888, a poly (ADP-ribose) polymerase inhibitor, and its metabolite in human plasma by liquid chromatography/tandem mass spectrometry.
A reversed-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of ABT-888 and its major metabolite (M8) in human plasma. Sample preparation involved a liquid-liquid extraction by the addition of 0.25 ml of plasma with 10 microl of 1 M NaOH and 1.0 ml ethyl acetate containing 50 ng/ml of the internal standard zileuton. The analytes were separated on a Waters XBridge C(18) column using a gradient mobile phase consisting of methanol/water containing 0.45% formic acid at the flow rate of 0.2 ml/min. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the ABT-888 and M8 concentration ranges of 1-2000 ng/ml in human plasma. The lower limits of quantitation (LLOQ) were 1 ng/ml for both ABT-888 and M8 in human plasma. The accuracy and within- and between-day precisions were within the generally accepted criteria for bioanalytical method (<15%). This method was successfully employed to characterize the plasma concentration-time profile of ABT-888 after its oral administration in cancer patients.
Wiegand
Richard
R
Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Wu
Jianmei
J
Sha
Xianyi
X
LoRusso
Patricia
P
Li
Jing
J
D001562:Benzimidazoles / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011786:Quality Control; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib