Analysis of deoxycytidine accumulation in gemcitabine treated patients

Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1225-32. doi: 10.1080/15257770600894642.

Abstract

Deoxycytidine (CdR) analogs are increasingly popular as chemotherapeutic agents and their effectiveness can be linked to the direct competition with active forms of endogenous CdR. A tandem mass spectrometric assay was developed to determine the plasma concentrations of CdR. Plasma extracts were prepared by protein precipitation and an ethyl acetate/water back extraction, and then separated chromatographically. Detection parameters were optimized for multi-reaction monitoring (MRM) tandem mass spectrometry and assay efficiency was improved using 15N3 CdR as an isotopic internal standard. Preliminary results from a gemcitabine trial are shown which indicate that CdR concentrations increase systemically during infusion, from about 5 nM to 78 nM after hepatic artery infusion and to 102 nM after systemic infusion for 24 hours. The developed assay demonstrated good sensitivity and selectivity for CdR.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Chemistry, Clinical / methods
  • Chromatography / methods
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / biosynthesis*
  • Deoxycytidine / blood
  • Deoxycytidine / pharmacokinetics*
  • Deoxycytidine / pharmacology
  • Humans
  • Mass Spectrometry
  • Models, Biological
  • Models, Chemical
  • Sensitivity and Specificity
  • Time Factors

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Deoxycytidine
  • gemcitabine