title: Analysis of deoxycytidine accumulation in gemcitabine treated patients.
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.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Honeywell
authors.forename: C J
authors.initials: CJ
authors.lastname: van Groeningen
authors.forename: A C
authors.initials: AC
authors.lastname: Laan
authors.forename: E
authors.initials: E
authors.lastname: Strocchi
authors.forename: R
authors.initials: R
authors.lastname: Ruiter
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002624:Chemistry, Clinical / Q000379:methods; D002845:Chromatography / Q000379:methods; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D008956:Models, Chemical; D012680:Sensitivity and Specificity; D013997:Time Factors; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000093542:Gemcitabine