title: Assay of urinary alpha-fluoro-beta-alanine by gas chromatography-mass spectrometry for the biological monitoring of occupational exposure to 5-fluorouracil in oncology nurses and pharmacy technicians.
abstract: The validation of an analytical method for the measurement of the unnatural amino acid alpha-fluoro-beta-alanine (AFBA), the main metabolite of the antineoplastic drug 5-fluorouracil (5FU), in urine for the biological monitoring of the exposure of hospital workers to the drug when preparing the therapeutical doses and administering to cancer patients is described. The method employed a two-step extractive derivatization of the analyte from urine to the N-trifluoroacety-n-butyl ester derivative and detection by selected-ion monitoring gas chromatography-mass spectrometry of structurally specific fragments. The limit of detection was 20 ng/mL with quantification accuracy better than +/-20% and precision (CV%) better than +/-20% in the range 0.020-10 microg/mL. Norleucine was used as the internal standard and the sample-to-sample analysis time was less than 15 min. The validated method has been applied to the biological monitoring of some hospital workers potentially exposed to 5FU and to matched control subjects. On a total number of 65 analyzed urine samples from control and exposed subjects, only three, obtained from exposed subjects, were found to be positive, with values of 20, 30 and 1150 ng/mL, respectively.
authors.affiliation: Department of Occupational Medicine, Clinica del Lavoro L. Devoto, Università degli Studi di Milano at Ospedale San Paolo, Italy. federico.rubino@unimi.it
authors.forename: Federico Maria
authors.initials: FM
authors.lastname: Rubino
authors.forename: Cinzia
authors.initials: C
authors.lastname: Verduci
authors.forename: Marina
authors.initials: M
authors.lastname: Buratti
authors.forename: Silvia
authors.initials: S
authors.lastname: Fustinoni
authors.forename: Laura
authors.initials: L
authors.lastname: Campo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Omodeo-Salè
authors.forename: Margherita
authors.initials: M
authors.lastname: Giglio
authors.forename: Sergio
authors.initials: S
authors.lastname: Iavicoli
authors.forename: Gabri
authors.initials: G
authors.lastname: Brambilla
authors.forename: Antonio
authors.initials: A
authors.lastname: Colombi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000652:urine*; D004784:Environmental Monitoring / Q000379:methods*; D005472:Fluorouracil / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D016273:Occupational Exposure; D009859:Oncology Nursing; D013678:Technology, Pharmaceutical; D000078329:Workforce; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015091:beta-Alanine; C032348:alpha-fluoro-beta-alanine; D005472:Fluorouracil