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. 2010 May 1;52(1):122-8.
doi: 10.1016/j.jpba.2009.12.015. Epub 2009 Dec 29.

A rapid and sensitive method for determination of veliparib (ABT-888), in human plasma, bone marrow cells and supernatant by using LC/MS/MS

Sarah Reinhardt  1 , Ming Zhao, Aleksander Mnatsakanyan, Linping Xu, Rebecca M Ricklis, Alice Chen, Judith E Karp, Michelle A Rudek
Affiliations

A rapid and sensitive method for determination of veliparib (ABT-888), in human plasma, bone marrow cells and supernatant by using LC/MS/MS

Sarah Reinhardt et al. J Pharm Biomed Anal. .

Abstract

A rapid and sensitive method was developed and validated using a liquid chromatographic method with tandem mass spectrometry detection (LC/MS/MS) for determination of veliparib (ABT-888) in plasma, bone marrow supernatant, and bone marrow cells. Sample preparation involved a single protein precipitation step by the addition of the sample with acetonitrile. Separation of veliparib and the internal standard, A620223.69, was achieved on a Atlantis dC(18) column (100mmx2.1mm, 3microm) column using a mobile phase consisting of acetonitrile-ammonium acetate (2mM) containing formic acid (0.1%, v/v) using isocratic flow at 0.2mL/min for 3min. The analyte and internal standard were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 5-1000nM. The values for both within day and between day precision and accuracy were well within the generally accepted criteria for analytical methods. This method was subsequently used to measure concentrations of veliparib in cancer patients receiving an oral daily dose of 10mg with demonstration of drug accumulation in the marrow compartment and in the target leukemia bone marrow cells.

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Figures

Figure 1
Figure 1
Full-scan product ion spectrum and chemical structure of veliparib with monitoring at m/z 245.2 → 162.2
Figure 2
Figure 2
Chromatogram of blank human (A) plasma, (B) bone marrow supernatant and (C) bone marrow cells
Figure 2
Figure 2
Chromatogram of blank human (A) plasma, (B) bone marrow supernatant and (C) bone marrow cells
Figure 2
Figure 2
Chromatogram of blank human (A) plasma, (B) bone marrow supernatant and (C) bone marrow cells
Figure 3
Figure 3
Chromatograms of internal standard (top panel) and veliparib (bottom panel) in blank (A) plasma, (B) bone marrow supernatant, and (C) bone marrow cells
Figure 3
Figure 3
Chromatograms of internal standard (top panel) and veliparib (bottom panel) in blank (A) plasma, (B) bone marrow supernatant, and (C) bone marrow cells
Figure 3
Figure 3
Chromatograms of internal standard (top panel) and veliparib (bottom panel) in blank (A) plasma, (B) bone marrow supernatant, and (C) bone marrow cells
Figure 4
Figure 4
Representative patient chromatograms of internal standard (top panel) and veliparib (bottom panel) (A) plasma C1D1 8 hr after veliparib administration, (B) bone marrow cells C1D4 5.25 hr after veliparib administration with 28 × 106 cell count, and (C) bone marrow supernatant C1D4 5.25 hr after veliparib administration.
Figure 4
Figure 4
Representative patient chromatograms of internal standard (top panel) and veliparib (bottom panel) (A) plasma C1D1 8 hr after veliparib administration, (B) bone marrow cells C1D4 5.25 hr after veliparib administration with 28 × 106 cell count, and (C) bone marrow supernatant C1D4 5.25 hr after veliparib administration.
Figure 4
Figure 4
Representative patient chromatograms of internal standard (top panel) and veliparib (bottom panel) (A) plasma C1D1 8 hr after veliparib administration, (B) bone marrow cells C1D4 5.25 hr after veliparib administration with 28 × 106 cell count, and (C) bone marrow supernatant C1D4 5.25 hr after veliparib administration.
Figure 5
Figure 5
Veliparib plasma concentration-time profile on day 1 in a patient receiving the first dose of 10 mg orally.
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