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.

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.
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DOI:
10.1016/j.jchromb.2008.07.032
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发表时间:
2008-09-01
影响因子:
3
通讯作者:
Beumer, Jan H.
Beumer, Jan H.
中科院分区:
医学3区
文献类型:
--
作者:
Parise, Robert A.;Shawaqfeh, Mohammad;Egorin, Merrill J.;Beumer, Jan H.

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ABT-888, a 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 1,000 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.
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