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一种通用的液相色谱-串联质谱法外显子组方法,用于测定生物基质中的外源性雌激素。

A Generic Liquid Chromatography-Tandem Mass Spectrometry Exposome Method for the Determination of Xenoestrogens in Biological Matrices.

机构信息

University of Vienna , Faculty of Chemistry, Department of Food Chemistry and Toxicology , Währingerstraße 38 , 1090 Vienna , Austria.

Epidemiology and Prevention Unit , Fondazione IRCCS Istituto Nazionale dei Tumori , 20133 Milan , Italy.

出版信息

Anal Chem. 2019 Sep 3;91(17):11334-11342. doi: 10.1021/acs.analchem.9b02446. Epub 2019 Aug 22.

Abstract

We are constantly exposed to a variety of environmental contaminants and hormones, including those mimicking endogenous estrogens. These highly heterogeneous molecules are collectively referred to as xenoestrogens and hold the potential to affect and alter the delicate hormonal balance of the human body. To monitor exposure and investigate potential health implications, comprehensive analytical methods covering all major xenoestrogen classes are needed but not available to date. Herein, we describe a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of multiple classes of endogenous as well as exogenous estrogens in human urine, serum, and breast milk to enable proper exposure and risk assessment. In total, 75 analytes were included, whereof a majority was successfully in-house validated in the three matrices. Extraction recoveries of validated analytes ranged from 71% to 110% and limits of quantification from 0.015 to 5 μg/L, 0.03 to 14 μg/L, and 0.03 to 4.6 μg/L in urine, serum, and breast milk, respectively. The applicability of the novel method was demonstrated in proof-of-principle experiments by analyzing urine from Austrian individuals and breast milk from Austrian and Nigerian individuals. Thereby, we proved the methods' feasibility to identify and quantify different classes of xenoestrogens simultaneously. The results illustrate the general importance of multiclass exposure assessment in the context of the exposome paradigm. Specifically, they highlight the need for estimating total estrogenic burden rather than single analyte or chemical class measurements and its potential impact in endocrine disruption and hormone related diseases including cancers.

摘要

我们不断暴露于各种环境污染物和激素之中,包括那些模拟内源性雌激素的物质。这些高度异质的分子被统称为外源性雌激素,它们有可能影响和改变人体微妙的激素平衡。为了监测暴露情况并研究潜在的健康影响,需要涵盖所有主要外源性雌激素类别的综合分析方法,但目前尚无此类方法。在此,我们描述了一种液相色谱-串联质谱(LC-MS/MS)方法,用于同时测定人尿液、血清和母乳中多种内源性和外源性雌激素,以进行适当的暴露和风险评估。总共包括 75 种分析物,其中大部分在这三种基质中都成功地进行了内部验证。经验证的分析物的提取回收率在 71%至 110%之间,定量限在尿液、血清和母乳中分别为 0.015 至 5μg/L、0.03 至 14μg/L 和 0.03 至 4.6μg/L。通过分析来自奥地利个体的尿液和来自奥地利和尼日利亚个体的母乳,在原理验证实验中证明了新方法的适用性。由此,我们证明了该方法同时识别和定量不同类外源性雌激素的可行性。结果表明在暴露组学范式背景下进行多类暴露评估的重要性。具体而言,它们强调了估计总雌激素负担而不是单个分析物或化学类别的测量及其在内分泌干扰和与激素相关疾病(包括癌症)中的潜在影响的必要性。

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