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Reliable quantification of 1,2-dihydroxynaphthalene in urine using a conjugated reference compound for calibration

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Abstract

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 D6-1,2-dihydroxynaphthalene (D6-1,2-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.

Reliable quantification of 1,2-dihydroxynaphthalene in urine using a conjugated reference compound for calibration

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Acknowledgements

We thank the German Federal Institute for Occupational Safety and Health (Bundesanstalt für Arbeitsschutz und Arbeitsmedizin) for the kindly provision of urine samples of exposed employees.

We are grateful to J. Bienert (MPI bpc) for recording 1H-NMR and mass-spectra and to Dr. H. Frauendorf and his co-workers (Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen) for HR-MS (ESI) of 1,2-DHN-Glc and D6-1,2-DHN-Glc.

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Authors and Affiliations

  1. Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Schillerstr. 25/29, 91054, Erlangen, Germany

    Melanie Zobel, Thomas Göen & Katrin Klotz

  2. Facility for Synthetic Chemistry, Max Planck Institute for Biophysical Chemistry (MPI bpc), Am Fassberg 11, 37077, Göttingen, Germany

    Vladimir Belov

Authors
  1. Melanie Zobel
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  2. Thomas Göen
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  4. Katrin Klotz
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Correspondence to Katrin Klotz.

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The authors declare to have no conflict of interests.

Human and animal rights and informed consent

Sample collection of workers urine was approved by the local ethics committee of the University of Erlangen-Nürnberg (Re.-No. 3997, 13.05.2009). Informed consent was obtained from all sample donors and they provided their urine voluntarily. No identifying information is included in this article.

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Zobel, M., Göen, T., Belov, V. et al. Reliable quantification of 1,2-dihydroxynaphthalene in urine using a conjugated reference compound for calibration. Anal Bioanal Chem 409, 6861–6872 (2017). https://doi.org/10.1007/s00216-017-0651-9

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  • DOI: https://doi.org/10.1007/s00216-017-0651-9

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