Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, 2610 Wilrijk, Belgium.
Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, 2610 Wilrijk, Belgium.
Talanta. 2019 Jun 1;198:230-236. doi: 10.1016/j.talanta.2019.02.024. Epub 2019 Feb 5.
Alternative plasticizers (APs) have been increasingly used in the last decade to replace conventional phthalate esters, in particular di(2-ethylhexyl) phthalate (DEHP), due to the toxicity of the latter. However, there is currently very little data about the toxicity of and exposure to APs. No method exists so far for the analysis of multiple exposure biomarkers. The objective of this work consisted in developing a simple bioanalytical procedure for the analysis of multiple exposure biomarkers of APs in human urine and serum. Focus was set on metabolites of di(2-propylheptyl) phthalate (DPrHpP), di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP) and di-2-ethylhexyl adipate (DEHA). A sample preparation protocol was developed and optimized using Oasis HLB solid-phase extraction (SPE) cartridges. Subsequently, an instrumental method based on liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) was optimized. Following established guidelines, the sample preparation and instrumental methods were validated in terms of recovery, matrix effects, carry-over, linearity, limits of quantification, within- and between-run precision and trueness. Obtained results were satisfactory for all compounds except for one of the metabolites of DEHA (i.e., mono(2-ethylhexyl) adipate (MEHA)). A pilot biomonitoring study was carried out to assess the method's ability to detect and quantify target analytes in human urine and serum. In urine, most analytes could be detected with frequencies ranging from 8% for mono(2-ethyl-5-hydroxyhexyl) adipate (OH-MEHA) and cyclohexane-1,2-dicarboxylic mono hydroxyisononyl ester (OH-MINCH) to 92% for mono(2-ethyl-5-oxohexyl) adipate (oxo-MEHA), whilst most compounds could not be detected in serum, except for mono(2-ethylhexyl) terephthalate (MEHTP) and mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPrHpP) which were detected in all samples. The obtained results show that the developed method can be used to simultaneously analyse multiple exposure biomarkers to APs in human urine and serum.
替代增塑剂（APs）在过去十年中由于邻苯二甲酸酯的毒性而越来越多地被用于替代传统的邻苯二甲酸酯，特别是邻苯二甲酸二（2-乙基己基）酯（DEHP）。然而，目前关于 APs 的毒性和接触的信息非常少。目前还没有分析多种接触生物标志物的方法。这项工作的目的是开发一种简单的生物分析程序，用于分析人尿液和血清中的多种 APs 接触生物标志物。重点是邻苯二甲酸二（2-丙基庚基）酯（DPrHpP）、二（异壬基）环己烷-1,2-二羧酸酯（DINCH）、邻苯二甲酸二（2-乙基己基）酯（DEHTP）和己二酸二（2-乙基己基）酯（DEHA）的代谢物。使用 Oasis HLB 固相萃取（SPE）小柱开发并优化了样品制备方案。随后，优化了基于液相色谱-串联质谱（LC-MS/MS）的仪器方法。根据既定准则，从回收率、基质效应、交叉污染、线性、定量下限、日内和日间精密度以及准确性等方面对样品制备和仪器方法进行了验证。除 DEHA 的一种代谢物（即单（2-乙基己基）己二酸酯（MEHA））外，所有化合物的结果均令人满意。进行了一项初步的生物监测研究，以评估该方法检测和定量人尿液和血清中目标分析物的能力。在尿液中，大多数分析物的检测频率从 8%（单（2-乙基-5-羟基己基）己二酸酯（OH-MEHA）和环己烷-1,2-二羧酸单羟基异壬基酯（OH-MINCH））到 92%（单（2-乙基-5-氧代己基）己二酸酯（oxo-MEHA）不等，而大多数化合物在血清中无法检测到，除了单（2-乙基己基）对苯二甲酸酯（MEHTP）和单（2-丙基-6-羟基庚基）邻苯二甲酸酯（OH-MPrHpP），这两种化合物在所有样本中均有检测到。结果表明，该方法可用于同时分析人尿液和血清中多种 APs 接触生物标志物。
