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Biomonitoring of occupational exposure to 5-fluorouracil by assaying α-fluoro-β-alanine in urine with a highly sensitive UHPLC-MS/MS method

Abstract

5-fluorouracil (5-FU) is one of the most frequently antineoplastic drugs handled by healthcare professionals. In order to monitor occupational exposure to 5-FU, a highly sensitive ESI-UHPLC-MS/MS method was developed for the assay of its main human metabolite α-fluoro-β-alanine (FBAL) in urine. After a derivatization step, extraction method consisted of solid phase extraction for the urinary. A good linearity (r>0.996), precision (CV<14.76%), and accuracy (bias<12,16%) were achieved. The lower limit of quantification (LOQ), 20pg/ml, is the lowest ever published. Applying this method in routine, more than 73 healthcare professionals occupationally exposed to 5-fluorouracil were monitored and 90 urines were analyzed. Seven healthcare professionals (9.6%) were found to be contaminated. Among analyzed urines, 7 samples were found positives. The FBAL measured concentrations ranged from 25 to 301pg/ml. Such efficient analytical tool combining high specificity with high sensitivity is essential for reliable detection and routine biological monitoring of healthcare professionals occupationally exposed to this widely used antineoplastic drug. This method allows biomonitoring of occupational exposure to 5-fluorouracil, to assess effectiveness of collective and individual protective measures.

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Publication details

The article was received on 15 Mar 2018, accepted on 29 Jun 2018 and first published on 11 Jul 2018


Article type: Paper
DOI: 10.1039/C8AN00479J
Citation: Analyst, 2018, Accepted Manuscript
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    Biomonitoring of occupational exposure to 5-fluorouracil by assaying α-fluoro-β-alanine in urine with a highly sensitive UHPLC-MS/MS method

    A. Dhersin, B. Atgé, B. Martinez, K. Titier, M. Rousset, M. Sidatt Cheikh El Moustaph , C. Verdun-Esquer, M. Molimard, A. Villa and M. Canal Raffin, Analyst, 2018, Accepted Manuscript , DOI: 10.1039/C8AN00479J

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