Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schillerstr. 25/29, 91054, Erlangen, Germany.
Facility for Synthetic Chemistry, Max Planck Institute for Biophysical Chemistry (MPI bpc), Am Fassberg 11, 37077, Göttingen, Germany.
Anal Bioanal Chem. 2017 Nov;409(29):6861-6872. doi: 10.1007/s00216-017-0651-9. Epub 2017 Oct 10.
After environmental and occupational exposure to naphthalene, 1,2-dihydroxynaphthalene (1,2-DHN) was shown to be one major metabolite in human naphthalene metabolism. However, the instability of free 1,2-DHN complicates the reliable determination of this promising biomarker in urine. To solve this stability problem, glucuronide conjugates of 1,2-DHN and the corresponding isotopically labelled D-1,2-dihydroxynaphthalene (D-1,2-DHN) were synthesised and applied as reference material and internal standard in a gas chromatographic-tandem mass spectrometric (GC-MS/MS) method. The determination of 1- and 2-naphthol (1-MHN, 2-MHN) was included in the procedure to enable a comprehensive assessment of naphthalene metabolism and exposure. The results of the validation showed a high reliability and sensitivity of the method. The detection limits range from 0.05 to 0.16 μg/L. Precision and repeatability were determined to range from 1.4 to 6.6% for all parameters. The simultaneous determination of 1- and 2-MHN as additional parameters besides 1,2-DHN enables the application of the method for further metabolism and kinetic studies on naphthalene. The use of glucuronide-derivative reference substances and the application of structurally matched isotopic-labelled internal standards for each substance guarantee a reliable quantification of the main naphthalene metabolites 1,2-DHN and 1- and 2-MHN. Graphical abstract Reliable quantification of 1,2-dihydroxynaphthalene in urine using a conjugated reference compound for calibration.
萘暴露于环境和职业环境后，1,2-二羟萘（1,2-DHN）被证明是人体萘代谢中的主要代谢物之一。然而，游离 1,2-DHN 的不稳定性使得在尿液中可靠地确定这一有前途的生物标志物变得复杂。为了解决这个稳定性问题，合成了 1,2-DHN 的葡萄糖醛酸缀合物及其相应的同位素标记的 D-1,2-二羟萘（D-1,2-DHN），并将其用作参考物质和内标物，应用于气相色谱-串联质谱（GC-MS/MS）方法中。该程序还包括对 1-和 2-萘酚（1-MHN，2-MHN）的测定，以全面评估萘的代谢和暴露情况。验证结果表明该方法具有很高的可靠性和灵敏度。检测限范围为 0.05 至 0.16μg/L。所有参数的精密度和重复性均在 1.4%至 6.6%之间。除 1,2-DHN 外，同时测定 1-MHN 和 2-MHN 作为其他参数，使该方法能够应用于萘的进一步代谢和动力学研究。葡萄糖醛酸衍生参考物质的使用和每种物质结构匹配的同位素标记内标物的应用保证了主要萘代谢物 1,2-DHN 以及 1-和 2-MHN 的可靠定量。
