Analysis of deoxycytidine accumulation in gemcitabine treated patients.
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.
Honeywell
R
R
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
van Groeningen
C J
CJ
Laan
A C
AC
Strocchi
E
E
Ruiter
R
R
Giaccone
G
G
Peters
G J
GJ
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
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000093542:Gemcitabine