Determination of 5-hydroxythiabendazole in human urine as a biomarker of exposure to thiabendazole using LC/MS/MS
Determination of 5-hydroxythiabendazole in human urine as a biomarker of exposure to thiabendazole using LC/MS/MS
复制标题
DOI：
10.1016/j.jchromb.2014.10.003
复制
发表时间：
2014-12-15
影响因子：
3
通讯作者：
Lindh, Christian H.
中科院分区：
文献类型：
--
作者：
Ekman, Eva;Faniband, Moosa H.;Lindh, Christian H.
噻苯达唑（TBZ）被广泛用作种植前和收获后的农业杀菌剂以及人类和动物的驱虫剂。由于在哺乳动物中报道了包括肾源性、肝源性、致畸性和神经系统效应在内的不良反应，TBZ引起了毒理学关注。职业接触可能发生在农业工人中，而一般公众也可能通过饮食在环境中接触到TBZ。选择代谢物5-羟基噻苯达唑（5-OH-TBZ）作为TBZ暴露的生物标志物，建立了LC/MS/MS定量测定人尿中5-OH-TBZ的方法。该方法包括酶水解，因为5-OH-TBZ与尿中的葡萄糖醛酸和硫酸盐结合。采用96孔板对样品处理和固相萃取（SPE）进行了优化。该方法具有优良的运行内、运行间和批间精密度，在4% ~ 9%之间。检测限（LOD）为0.05，定量限（LOQ）为0.13 ng 5-OH-TBZ/mL尿液，可在环境暴露人群中检测到。当将该方法应用于瑞典一般人群时，52%的人的水平高于LOD。该方法还应用于两个人的口服和皮肤人体实验暴露研究。口服暴露后，尿中5-OH-TBZ的排泄由双室模型描述，第一个快速和第二个较慢的消除阶段都遵循一级动力学，估计消除半衰期为2小时和9-12小时。尿中的回收率在剂量的21%至24%之间。皮肤暴露由一室模型描述，并遵循一级动力学，估计消除半衰期为9-18小时。尿液中的回收率为给药剂量的1%。虽然这些研究仅限于两个人，但这些数据提供了关于口服和皮肤暴露后TBZ毒性动力学的新的基本信息。(C) 2014年作者。Elsevier B.V.出版
Thiabendazole (TBZ) is widely used as a pre-planting and post-harvest agricultural fungicide and as an anthelminthic in humans and animals. TBZ is of toxicological concern, since adverse effects including nephrogenic, hepatogenic, teratogenic and neurological effects have been reported in mammals. Occupational exposure can occur among agricultural workers and the general public may be environmentally exposed to TBZ through the diet. The metabolite 5-hydroxythiabendazole (5-OH-TBZ) was chosen as biomarker of exposure to TBZ and a LC/MS/MS method for the quantification of 5-OH-TBZ in human urine was developed. The method includes enzyme hydrolysis, as 5-OH-TBZ is conjugated to glucuronide and sulphate in urine. Sample through put was optimised using 96-well plates for sample handling as well as for solid phase extraction (SPE). The method has excellent, within-run, between-run and between-batch precision between 4 and 9%. The limit of detection (LOD) of 0.05 and a limit of quantification (LOQ) of 0.13 ng 5-OH-TBZ/mL urine enable detection in environmentally exposed populations. When applying the method in a general Swedish population, 52% had levels above LOD. The method was also applied in one oral and one dermal human experimental exposure study in two individuals. After oral exposure, the excretion of 5-OH-TBZ in urine was described by a two-compartment model and both the first rapid and the second slower elimination phase followed first-order kinetics, with estimated elimination half-life of 2 h and 9-12 h. The recoveries in urine were between 21 and 24% of the dose. Dermal exposure was described by a one compartment model and followed first order kinetics, with estimated elimination half-life of 9-18 h. The recovery in urine was 1% of the administrated dose of TBZ. Although these studies are limited to two individuals, the data provide new basic information regarding the toxicokinetics of TBZ after oral and dermal exposure. (C) 2014 The Authors. Published by Elsevier B.V.