Département Polluants et Santé, Institut National de Recherche et de Sécurité, rue du Morvan, CS 60027, 54519 Vandoeuvre cedex, France.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 1;878(27):2630-4. doi: 10.1016/j.jchromb.2010.02.011. Epub 2010 Feb 17.
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.
一种新的灵敏且特异的 HPLC-MS/MS 方法，用于测定尿中氟尿嘧啶（5-FU）的主要代谢物α-氟-β-丙氨酸（FBAL），以进行接触 5-FU 的医护人员的生物监测调查。该方法的特点是通过 2,4-二硝基氟苯进行柱前 FBAL 衍生化，然后进行固相萃取样品净化。通过亲水作用色谱（HILIC）在 ZIC HILIC 柱（Sequant）上实现色谱分离，通过串联质谱进行定量。该方法具有高灵敏度，定量限为 1μg/l，优于以往报道的方法。在 LOQ 时，日内和日间精密度分别小于 13%和 15%，且未观察到 FBAL 的显著相对基质效应。该验证方法应用于法国一家医院的职业接触 5-FU 的生物监测。在医院药房和肿瘤科病房，19 名工作人员在 5 天内采集了班前和班后尿样。在总共分析的 121 个样本中，高达 29%的样本中检测到可测量量的 FBAL，浓度范围从定量限到 22.7μg/l，证明存在职业接触 5-FU 的情况。此类数据很少，代表着在评估与处理抗肿瘤药物相关的职业健康风险方面迈出了一步。
