LC-MS-MS Analysis of Urinary Biomarkers of Imazalil Following Experimental Exposures.
LC-MS-MS Analysis of Urinary Biomarkers of Imazalil Following Experimental Exposures.
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DOI：
10.1093/jat/bkv100
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发表时间：
2015-11
影响因子：
2.5
通讯作者：
Lindh CH
中科院分区：
文献类型：
--
作者：
Faniband MH;Littorin M;Ekman E;Jönsson BA;Lindh CH
抑霉唑（IMZ）是一种杀真菌剂，用于蔬菜（如黄瓜）的种植，在绿色温室或水果收获后，以避免由于真菌生长而腐败。农业工人可能因职业接触IMZ，一般公众也可能因饮食间接接触IMZ。本研究的目的是开发和验证用于分析人尿液中IMZ的LC-MS-MS方法。该方法采用电喷雾离子化和选择性反应监测的积极模式。在0.5-100 ng/mL范围内观察到良好的线性。该方法的检测限为0.2 ng/mL，定量限为0.8 ng/mL。该方法具有良好的批内、批间和批间精密度，变异系数<15%。该方法被应用于分析尿液样品从两个人类志愿者实验口服和皮肤接触后。IMZ的排泄符合二室模型和一级动力学。在口服暴露中，女性和男性志愿者IMZ在快速排泄相的消除半衰期分别为2.6和1.9 h。在缓慢排泄期，分别为7.6和13小时。经皮给药的排泄符合单室模型和一级动力学。女性和男性志愿者的消除半衰期分别为10和6.6 h。虽然该研究仅限于两名志愿者，但提供了IMZ在人体内的基本毒代动力学和代谢信息。
Imazalil (IMZ) is a fungicide used in the cultivation of vegetables, such as cucumbers, in green houses or post-harvest on fruit to avoid spoilage due to fungal growth. Agricultural workers can be occupationally exposed to IMZ and the general public indirectly by the diet. The purpose of this study was to develop and validate an LC–MS-MS method for the analysis of IMZ in human urine. The method used electrospray ionization and selected reaction monitoring in the positive mode. Excellent linearity was observed in the range 0.5–100 ng/mL. The limit of detection of the method was 0.2 ng/mL, and the limit of quantitation 0.8 ng/mL. The method showed good within-run, between-run and between-batch precision, with a coefficient of variation <15%. The method was applied to analyze urine samples obtained from two human volunteers following experimental oral and dermal exposure. The excretion of IMZ seemed to follow a two-compartment model and first-order kinetics. In the oral exposure, the elimination half-life of IMZ in the rapid excretion phase was 2.6 and 1.9 h for the female and the male volunteer, respectively. In the slower excretion phase, it was 7.6 and 13 h, respectively. In the dermal exposure, the excretion seemed to follow a single-compartment model and first-order kinetics. The elimination half-life was 10 and 6.6 h for the female and the male volunteer, respectively. Although the study is limited to two volunteers, some information on basic toxicokinetics and metabolism of IMZ in humans is presented.