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. 2009 Jan;32(2):261-272.
doi: 10.1080/10826070802603351.

Liquid Chromatographic Determination of NSC 737664 (ABT-888: an Inhibitor of Poly(ADP-ribose) Polymerase (PARP)) in Plasma and Urine in a Phase 0 Clinical Trial

Lawrence R Phillips  1 , Kimberly D Hill, Eva Majerova
Affiliations

Liquid Chromatographic Determination of NSC 737664 (ABT-888: an Inhibitor of Poly(ADP-ribose) Polymerase (PARP)) in Plasma and Urine in a Phase 0 Clinical Trial

Lawrence R Phillips et al. J Liq Chromatogr Relat Technol. 2009 Jan.

Abstract

A gradient reversed-phase high performance liquid chromatographic method was developed for determining NSC 737664 (2-[(2R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide; ABT-888) in human plasma and urine. Chromatographic separation used a mobile phase composed of 0.1% formic acid in water and 0.1% formic acid in acetonitrile, and a C18 column (150 mm × 4.6 mm, 5µ). Quantitation was performed using UV detection at 300 nm. Chromatographic peak identity was confirmed using positive-ion electrospray ionization mass spectrometry. The method was shown to be specific, accurate and reproducible, and thereby appropriate for monitoring plasma and urine levels of the agent in support of a phase 0 clinical study.

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Figures

Figure 1
Figure 1
Chemical structure of NSC 737664 (ABT-888).
Figure 2
Figure 2
Time-selected detector response vs. time profiles reconstructed from data acquired during liquid chromatographic separation: (A) UV absorbance at 300 nm of an extract of human plasma to which only the internal standard had been added, and (B) of an extract of human plasma spiked with NSC 737664 at a concentration of 2.5 µM; (C) extracted ion detection (m⁠/⁠z 245) of an extract of human plasma to which only the internal standard had been added, and (D) of an extract of human plasma spiked at a concentration of 2.5 µM. Peak Assignments: 1, internal standard; 2, NSC 737664.
Figure 3
Figure 3
Plasma Concentration vs. Time Profile of NSC 737664 (ABT-888) in a Participant of a Phase 0 Clinical Study Following a Single, Oral Dose of 50 mg.
See this image and copyright information in PMC

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