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Journal Article

A novel method for the accurate quantification of two isomeric mercapturic acids of 1,3-dichlorobenzene in human urine using isotope dilution online-SPE-LC-MS/MS


Belov,  Vladimir N.       
Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Schettgen, T., Belov, V. N., Kraus, T., & Ziegler, P. (2024). A novel method for the accurate quantification of two isomeric mercapturic acids of 1,3-dichlorobenzene in human urine using isotope dilution online-SPE-LC-MS/MS. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1234: 124034. doi:10.1016/j.jchromb.2024.124034.

Cite as: https://hdl.handle.net/21.11116/0000-000F-1B42-9
1,3-dichlorobenzene (1,3-DCB) is an aromatic solvent that might be formed during thermal decomposition of bis(2,4-dichlorobenzoyl)peroxide used as initiator in silicone rubber production with many workers exposed worldwide. During metabolism of 1,3-DCB, two isomeric mercapturic acids can be formed from ring oxidation of 1,3-DCB in the liver, namely 2,4-dichlorophenylmercapturic acid (24CPhMA) and 3,5-dichlorophenylmercapturic acid (35CPhMA). These urinary mercapturic acids might serve as biomarkers of the toxicologically relevant absorbed dose of 1,3-DCB and have not been determined so far. Thus, we were aimed to develop an analytical method for quantification of these biomarkers.

Authentic standards of both mercapturic acids as well as deuterium-labelled analogues were self-synthesized. A method for the quantification of both CPhMAs in human urine using online-SPE LC/MS/MS was developed and validated with an LOQ of 0.1 ng mL−1 for both CPhMAs. The analytes were extracted from urine by online-SPE on a restricted access material phase, transferred to the analytical column and quantified by tandem mass spectrometry. Interday (n = 6) and Intraday (n = 10) precision for both CPhMAs ranged from 1.7 to 4.3 % with accuracies between 99.4 and 109.9 % at concentrations of 0.6 and 3 ng mL−1. We applied the method on post-shift urine samples of 16 workers of the silicone rubber industry with occupational exposure to 1,3-DCB. Both CPhMAs were above LOQ in 15 of 16 urine samples with median levels (range) for 24CPhMA and 35CPhMA of 1.64 ng mL−1 (<0.1 – 8.2 ng mL−1) and 3.98 ng mL−1 (0.36 – 24.1 ng mL−1), respectively.

This is the first report on specific urinary mercapturic acids of 1,3-DCB in humans. Our results show that ring oxidation of 1,3-DCB is considered to be a toxicologically relevant metabolic pathway in humans. This might improve risk assessment of 1,3-DCB-emissions in silicone rubber industry.