title: Decitabine triphosphate levels in peripheral blood mononuclear cells from patients receiving prolonged low-dose decitabine administration: a pilot study.
abstract: OBJECTIVE
  Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients.
  
  
  METHODS
  This article describes a method for the quantitative determination of decitabine triphosphate in PBMCs using liquid chromatography coupled to tandem mass spectrometry. The method was applied to ex vivo incubated whole blood samples and samples from three patients receiving prolonged low-dose decitabine treatment.
  
  
  RESULTS
  We successfully quantitated decitabine triphosphate in PBMCs. Considerable levels were detected in PBMCs from two patients that responded well to therapy, whereas only low levels were present in a non-responding patient. Moreover, the data show that, in contrast to plasma decitabine, intracellular decitabine triphosphate accumulates during a treatment cycle of nine infusions at a dose of 15 mg/m(2).
  
  
  CONCLUSIONS
  The results suggest a relationship between decitabine triphosphate levels and response to therapy. Based on the observed accumulation of decitabine triphosphate during a treatment cycle, a less intensive dose scheme could be feasible.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands. Robert.jansen@slz.nl
authors.forename: Robert S
authors.initials: RS
authors.lastname: Jansen
authors.forename: Hilde
authors.initials: H
authors.lastname: Rosing
authors.forename: Pierre W
authors.initials: PW
authors.lastname: Wijermans
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Keizer
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000378:metabolism*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D002853:Chromatography, Liquid; D000077209:Decitabine; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects; D053719:Tandem Mass Spectrometry
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine