title: Biological monitoring of occupational exposure to 5-fluorouracil: urinary α-fluoro-β-alanine assay by high performance liquid chromatography tandem mass spectrometry in health care personnel.
abstract: A new sensitive and specific HPLC-MS/MS method for the determination of α-fluoro-β-alanine (FBAL), the main metabolite of the antineoplastic drug 5-fluorouracil (5-FU), in urine for the biological monitoring survey of health care workers exposed to 5-FU is described. This procedure is characterized by a pre-column FBAL derivatization by 2,4-dinitrofluorobenzene followed by solid phase extraction sample clean-up. The chromatographic separation was achieved by hydrophilic interaction chromatography (HILIC) on a ZIC HILIC column (Sequant) and the quantification was performed by tandem mass spectrometry. The method offers high sensitivity with a quantification limit of 1 μg/l, which is an improvement on those previously reported. The within- and between-day precisions were less than 13% and 15% respectively at the LOQ and no significant relative matrix effect was observed for FBAL. The validated method was applied to the biological monitoring of occupational exposure to 5-FU in a French hospital. Pre- and post-shift urine samples were collected from 19 workers in a hospital pharmacy and an oncology ward over a period of 5 days. On a total of 121 analysed samples, measurable amounts of FBAL were detected in up to 29%, the concentrations range from LOQ to 22.7 μg/l, yielding evidence of occupational exposure to 5-FU. Such data are scarce and represent a step forward in assessing the occupational health risks associated with handling antineoplastic drugs.
authors.affiliation: Département Polluants et Santé, Institut National de Recherche et de Sécurité, rue du Morvan, CS 60027, 54519 Vandoeuvre cedex, France. sophie.ndaw@inrs.fr
authors.forename: S
authors.initials: S
authors.lastname: Ndaw
authors.forename: F
authors.initials: F
authors.lastname: Denis
authors.forename: P
authors.initials: P
authors.lastname: Marsan
authors.forename: A
authors.initials: A
authors.lastname: d'Almeida
authors.forename: A
authors.initials: A
authors.lastname: Robert
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004784:Environmental Monitoring / Q000379:methods*; D005472:Fluorouracil / Q000009:adverse effects / Q000652:urine*; D006282:Health Personnel; D006801:Humans; D057230:Limit of Detection; D016273:Occupational Exposure; D053719:Tandem Mass Spectrometry / Q000379:methods*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015091:beta-Alanine; C032348:alpha-fluoro-beta-alanine; D005472:Fluorouracil