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Assay of urinary α ‐fluoro‐ β ‐alanine by gas chromatography–mass spectrometry for the biological monitoring of occupational exposure to 5‐fluorouracil in oncology nurses and pharmacy technicians
Author(s) -
Rubino Federico Maria,
Verduci Cinzia,
Buratti Marina,
Fustii Silvia,
Campo Laura,
OmodeoSalè Emanuela,
Giglio Margherita,
Iavicoli Sergio,
Brambilla Gabri,
Colombi Antonio
Publication year - 2006
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.559
Subject(s) - chemistry , chromatography , urine , derivatization , mass spectrometry , analyte , detection limit , metabolite , gas chromatography–mass spectrometry , selected ion monitoring , gas chromatography , biochemistry
The validation of an analytical method for the measurement of the unnatural amino acid α ‐fluoro‐ β ‐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 µg/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. Copyright © 2005 John Wiley & Sons, Ltd.