CHU Clermont-Ferrand, Université Clermont-Auvergne, service de Pharmacologie médicale, UMR INSERM 1107 Neuro-Dol, F-63000 Clermont-Ferrand, France.
CHU Clermont-Ferrand, Université Clermont-Auvergne, service de Pharmacologie médicale, UMR INSERM 1107 Neuro-Dol, F-63000 Clermont-Ferrand, France; CHU Clermont-Ferrand, Délégation Recherche Clinique & Innovation, F-63000 Clermont-Ferrand, France.
Talanta. 2019 Jun 1;198:377-389. doi: 10.1016/j.talanta.2019.01.115. Epub 2019 Feb 6.
DiEthylHexylPhthalate (DEHP) can leach out of plasticized PVC medical devices (MD) and may enter into contact with patients. This phthalate is known for its reprotoxic and endocrine disrupting effects. Its use in medical devices (MD) has been restricted and alternative plasticizers have been developed. Nevertheless, no published clinical studies exist concerning patient exposure to these alternative plasticizers during medical care. This is particularly worrisome when high-risk populations, such as newborns, are exposed to these new plasticizers in intensive care units. Our study aimed to develop a novel sensitive and selective method to simultaneously identify and quantify DEHP and 17 other plasticizer metabolites (free or glucuronide conjugates), which are specific biomarkers of DEHTP, TOTM, DINP, DINCH and DEHA exposure in human urine. This robust method uses turbulent-flow online extraction technology coupled to high performance liquid chromatography - tandem mass spectrometry. Special care was taken to address two major problems in plasticizer analysis: contamination and chromatographic separation of interfering analogue structures. The validation was assessed in synthetic urine and the linearity of response was demonstrated for all compounds (R > 0.99), with limits of quantification from 0.01 to 0.1 ng/ml. Accuracies ranged from 86% to 117% and inter- and intra-day precisions were <20%. The clinical applicability and suitability of our new method was assessed in patients in a neonatal intensive care unit to measure urinary concentrations of DEHP and alternative plasticizer metabolites. These metabolites were found in the majority of urine samples, with a median detection frequency of 95.2% (ranging from 12.5% to 100%). The high sensitivity, selectivity and ruggedness make the method suitable for large-scale biomonitoring studies of high-risk and general populations.
邻苯二甲酸二（2-乙基己基）酯（DEHP）可从增塑聚氯乙烯医疗器械（MD）中浸出，并可能与患者接触。这种邻苯二甲酸酯以其生殖毒性和内分泌干扰作用而闻名。它在医疗器械（MD）中的使用已受到限制，并开发了替代增塑剂。然而，目前尚无关于在医疗护理过程中患者接触这些替代增塑剂的临床研究。当高危人群（如新生儿）在重症监护病房中接触到这些新型增塑剂时，情况尤其令人担忧。我们的研究旨在开发一种新的灵敏和选择性方法，以同时识别和定量 DEHP 和其他 17 种增塑剂代谢物（游离或葡萄糖醛酸缀合物），这些代谢物是 DEHTP、TOTM、DINP、DINCH 和 DEHA 暴露于人体尿液中的特异性生物标志物。该强大方法使用湍流流在线提取技术与高效液相色谱 - 串联质谱法相结合。特别注意解决增塑剂分析中的两个主要问题：污染和干扰类似物结构的色谱分离。在合成尿液中评估了验证，并证明了所有化合物的响应线性（R > 0.99），定量下限为 0.01 至 0.1 ng/ml。准确度范围为 86%至 117%，日内和日间精密度均<20%。我们的新方法在新生儿重症监护病房的患者中评估了其临床适用性和适宜性，以测量尿液中 DEHP 和替代增塑剂代谢物的浓度。这些代谢物在大多数尿液样本中均有发现，中位数检出频率为 95.2%（范围为 12.5%至 100%）。该方法具有高灵敏度、选择性和坚固性，适合高危和一般人群的大规模生物监测研究。
