| 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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MedLine Citation:
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PMID: 18692448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ABT-888, a poly(ADP-ribose) polymerase (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 1000 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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Authors:
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Robert A Parise; Mohammad Shawaqfeh; Merrill J Egorin; Jan H Beumer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-07-31 |
Journal Detail:
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Title: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Volume: 872 ISSN: 1570-0232 ISO Abbreviation: J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-08-26 Completed Date: 2008-10-28 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 101139554 Medline TA: J Chromatogr B Analyt Technol Biomed Life Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 141-7 Citation Subset: IM |
Affiliation:
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Molecular Therapeutics, Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Benzimidazoles / administration & dosage, blood*, pharmacokinetics Calibration Chromatography, Liquid / methods* Enzyme Inhibitors / administration & dosage, blood*, pharmacokinetics Humans Poly(ADP-ribose) Polymerases / antagonists & inhibitors* Reference Standards Reproducibility of Results Sensitivity and Specificity Spectrometry, Mass, Electrospray Ionization / methods* |
| Grant Support | |
ID/Acronym/Agency:
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2P30CA47904/CA/NCI NIH HHS; P30 CA047904-219021/CA/NCI NIH HHS; U01 CA099168-05/CA/NCI NIH HHS; U01 CA099168-06/CA/NCI NIH HHS; U01CA099168/CA/NCI NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 RR024153/RR/NCRR NIH HHS; UL1 RR024153-01/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-((R)-2-methylpyrrolidin-2-yl)-1H-benzimidazole-4-carboxamide; 0/Benzimidazoles; 0/Enzyme Inhibitors; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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