Characterization of decomposition products and preclinical and low dose clinical pharmacokinetics of decitabine (5-aza-2'-deoxycytidine) by a new liquid chromatography/tandem mass spectrometry quantification method

Rapid Communications in Mass Spectrometry : RCM
Zhongfa LiuKenneth K Chan

Abstract

Aberrant DNA methylation patterns resulting in gene transcriptional repression are observed in numerous cancers. Decitabine, a DNA methyltransferase inhibitor, is being clinically evaluated in patients with hematologic malignancies and solid tumors. Decitabine is rather unstable and decomposes to 1-beta-D-2'-deoxyribofuranosyl-3-guanylurea under basic conditions and several additional unknown products under neutral conditions. This has greatly limited application of pharmacokinetic assays to clinical development of decitabine. In this paper, a high-performance liquid chromatography/ultraviolet multi-stage mass spectrometry (HPLC-UV-MSn) study of the decomposition of decitabine in water and human plasma revealed that these previously unknown products are isomers of the intermediates formyl-1-beta-D-2'-deoxyribofuranosyl-3-guanylurea and 1-beta-D-2'-deoxyribofuranosyl-3-guanylurea. A HPLC tandem mass spectrometry (MS/MS) method for the determination of decitabine concentrations in human and rat plasma has been developed. This method was based on a specific fragmentation pathway of the molecular ion of decitabine at m/z 229 to generate a unique fragment ion at m/z 113 under collision-induced dissociation. Separation of decitabine ...Continue Reading

References

Jan 1, 1985·Pharmacology & Therapeutics·R L MomparlerM Gyger
Jan 1, 1985·Pharmacology & Therapeutics·R L Momparler
Jan 1, 1985·European Journal of Cancer & Clinical Oncology·J M Covey, D S Zaharko
Nov 1, 1981·Journal of Pharmaceutical Sciences·K T LinG E Rivard
Jan 1, 1981·Leukemia Research·G E RivardL F Momparler
May 1, 1982·Journal of Cellular Physiology·S M Taylor, P A Jones
Jan 1, 1981·Drug and Chemical Toxicology·R L Momparler, C H Frith
Nov 1, 1995·British Journal of Haematology·N TuzunerJ M Bennett
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·C LiuR V Chari
Mar 1, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·P WijermansA Ferrant
Apr 3, 2001·Annals of Internal Medicine·V SantiniJ P Issa
Jul 23, 2003·Chemical Research in Toxicology·Zhongfa LiuLawrence M Sayre
Oct 10, 2003·Oncogene·Agnes Sze Wah ChanSuet Yi Leung
Nov 25, 2003·The New England Journal of Medicine·James G Herman, Stephen B Baylin
Jan 21, 2004·Cancer Letters·Shuji SugimotoKoichi Nagasaki
Apr 6, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·M ZillyH Klinker
Nov 24, 2004·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Ming ZhaoSharyn D Baker

❮ Previous
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Citations

Oct 29, 2008·Oncogene·B EwaldW Plunkett
Apr 28, 2007·The Cancer Journal·Bodo BruecknerFrank Lyko
Jan 5, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Reda Z MahfouzYogen Saunthararajah
May 24, 2014·PloS One·Ilaria NaldiCaterina Cinti
Jan 9, 2015·Drug Metabolism Reviews·Lisa Pleyer, Richard Greil
Apr 20, 2011·Expert Opinion on Drug Metabolism & Toxicology·Jeffrey BryanElias Jabbour
Feb 2, 2013·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Youxi ZhangZhonggui He
Nov 10, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yonghua LingZhongfa Liu
Aug 8, 2009·Journal of Pharmaceutical and Biomedical Analysis·Anna ArgemíJavier Saurina
Jun 17, 2008·Bioorganic & Medicinal Chemistry·Martin DracínskýAntonín Holý
Jan 29, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Katan PatelDuncan I Jodrell
Nov 15, 2006·Journal of Mass Spectrometry : JMS
Apr 22, 2008·International Journal of Cancer. Journal International Du Cancer·Carlo Stresemann, Frank Lyko
Jul 29, 2011·International Journal of Cancer. Journal International Du Cancer·Oscar AlcazarPierre Triozzi
Oct 15, 2013·Bioorganic & Medicinal Chemistry·Jonathan M RawsonLouis M Mansky
May 26, 2012·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Haiyan XuBo Yuan
Jun 23, 2016·Clinical Epigenetics·Jeannine DieschKatharina S Götze
Aug 30, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Wenyi HuaDaniel Mulvana
Aug 8, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·William BlumGuido Marcucci
Mar 19, 2014·International Journal of Toxicology·Pramod TerseJoseph M Covey
Sep 3, 2013·Antiviral Chemistry & Chemotherapy·Christine L ClouserSteven E Patterson
Aug 19, 2015·Antimicrobial Agents and Chemotherapy·Jonathan M O RawsonLouis M Mansky
Oct 27, 2015·Journal of Hematology & Oncology·Seunghoon HanDong-Seok Yim
Oct 13, 2019·Investigational New Drugs·Jeroen RoosendaalAram Oganesian
Feb 1, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anastasios StathisLillian L Siu

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