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Simultaneous determination of ABT-888, a poly (ADP-ribose) polymerase inhibitor, and its metabolite in human plasma by liquid chromatography/tandem mass spectrometry.

Author(s): Wiegand R, Wu J, Sha X, LoRusso P, Li J

Affiliation(s): Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.

Publication date & source: 2010-02-01, J Chromatogr B Analyt Technol Biomed Life Sci., 878(3-4):333-9. Epub 2009 Nov 27.

Publication type: Clinical Trial; Research Support, N.I.H., Extramural

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. 2009 Elsevier B.V. All rights reserved.

Page last updated: 2010-10-05

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