title: Determination of 5-fluorouracil in plasma with HPLC-tandem mass spectrometry.
abstract: In this article, we describe a fast and specific method to measure 5FU with HPLC tandem-mass spectrometry. Reversed-phase HPLC was combined with electrospray ionization tandem mass spectrometry and detection was performed by multiple-reaction monitoring. Stable-isotope-labeled 5FU (1,3-15N2-5FU) was used as an internal standard. 5FU was measured within a single analytical run of 16 min with a lower limit of detection of 0.05 microM. The intra-assay variation and inter-assay variation of plasma with added 5FU (1 microM, 10 microM, 100 microM) was less then 6%. Recoveries of the added 5FU in plasma were > 97%. Analysis of the 5FU levels in plasma samples from patients with the HPLC tandem mass spectrometry method and a HPLC-UV method yielded comparable results (r2 = 0.98). Thus, HPLC with electrospray ionization tandem mass spectrometry allows the rapid analysis of 5FU levels in plasma and could, therefore, be used for therapeutic drug monitoring.
authors.affiliation: Academic Medical Center, University of Amsterdam, Emma Children's Hospital and Department of Clinical Chemistry, Amsterdam, The Netherlands. a.b.vankuilenburg@amc.uva.nl
authors.forename: A B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.forename: H
authors.initials: H
authors.lastname: van Lenthe
authors.forename: J G
authors.initials: JG
authors.lastname: Maring
authors.forename: A H
authors.initials: AH
authors.lastname: van Gennip
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013997:Time Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil