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A validated UPLC–MS/MS method for biomonitoring the exposure to the fragrance 7-hydroxycitronellal
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2017-10-26 , DOI: 10.1016/j.jchromb.2017.10.040
Markus Stoeckelhuber , Dusan Krnac , Nikola Pluym , Max Scherer , Edgar Leibold , Gerhard Scherer

7-Hydroxycitronellal is a synthetic fragrance (CAS No. 107-75-5) which is used commonly in cosmetics, washing- and cleaning agents and as flavoring in foods. Due to its broad application in various fields, 7-hydroxycitronellal was selected for the development of a biomonitoring method for the quantitative exposure assessment within the frame of the cooperation project of the German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI). For this purpose, an ultra performance liquid chromatography combined with tandem mass spectrometry (UPLC–MS/MS) based method was developed for the determination of potential biomarkers of 7-hydroxycitronellal (7-HC) in human urine samples. 7-Hydroxycitronellylic acid (7-HCA) turned out to be the quantitatively most important metabolite of 7-HC in human urine, occurring in 1000 times higher amounts than 7-hydroxycitronellol (7-HCO) or other potential metabolites. Therefore, an analytical method for 7-HCA was developed using stable isotope-labeled 7-HCA as internal standard (IS). The method includes a cleavage step of possible metabolite conjugates with an enzyme mix of ß-glucuronidase and arylsulfatase. Subsequent sample cleanup was performed by liquid–liquid extraction (LLE) with dichloromethane. The method was calibrated by calculating the linear regression between the analyte/IS ratio and the nominal 7-HCA concentrations in water. The method was validated according to approved standard guidelines and proved to be robust, reliable and sensitive for the human biomonitoring of 7-HC. The method was applied to urine samples of 40 adult volunteers from the general population. 7-HCA was quantifiable in urine of all subjects. Thus the developed method proved to be suitable for assessing the background exposure to 7-HC in the general population.



中文翻译:

一种经过验证的UPLC-MS / MS方法,用于生物监测香料7-羟基香茅醛的暴露

7-羟基香茅醛是一种合成香料(CAS号107-75-5),通常用于化妆品,洗涤剂和清洁剂中以及在食品中用作调味剂。由于其在各个领域的广泛应用,在德国联邦环境,自然保护,建筑和核安全部( BMUB)和德国化学工业协会(VCI)。为此,开发了一种基于高效液相色谱结合串联质谱法(UPLC–MS / MS)的方法,用于测定人尿液样品中7-羟基香茅醛(7-HC)的潜在生物标记。事实证明7-羟基香柠檬酸(7-HCA)是人类尿液中7-HC的最重要的代谢产物,其含量是7-羟基香茅醇(7-HCO)或其他潜在代谢产物的1000倍。因此,开发了一种使用稳定同位素标记的7-HCA作为内标(IS)的7-HCA分析方法。该方法包括用β-葡萄糖醛酸苷酶和芳基硫酸酯酶的酶混合物裂解可能的代谢物缀合物的步骤。随后的样品净化是通过用二氯甲烷进行液-液萃取(LLE)进行的。通过计算分析物/ IS比率与水中名义7-HCA浓度之间的线性回归来校准该方法。该方法已根据批准的标准指南进行了验证,并被证明对7-HC的人体生物监测具有鲁棒性,可靠性和敏感性。该方法应用于来自普通人群的40名成人志愿者的尿液样本。所有受试者的尿液中7-HCA均可定量。因此,开发的方法被证明适用于评估普通人群中7-HC的背景暴露。

更新日期:2017-10-26
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