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High-resolution mass spectrometry provides novel insights into products of human metabolism of organophosphate and brominated flame retardants

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Abstract

The high resolution, accurate mass, and fast scanning features of the OrbitrapTM mass spectrometer, combined with the separation power of ultrahigh-performance liquid chromatography were applied for the first time to study the metabolic profiles of several organic flame retardants (FRs) present in indoor dust. To mimic real-life exposure, in vitro cultured HepG2 human hepatocyte cell lines were exposed simultaneously to various FRs in an indoor dust extract for 24 h. Target parent FRs, hexabromocyclododecanes (α-, β-, and γ-HBCDs), tris-2-chloroethyl phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), were separated in a single run for the first time using alternating positive and negative heated ESI source. Further metabolite separation and identification was achieved using full scan (70,000 full width at half maximum (FWHM)), accurate mass (up to 1 ppm) spectrometry. Structural confirmation was performed via all ion fragmentation (AIF) spectra using the optional higher collisional dissociation (HCD) cell and MS/MS analysis. First insights into human metabolism of HBCDs revealed several hydroxylated and debrominated phase I metabolites, in addition to conjugated phase II glucuronides. Furthermore, various hydroxylated, oxidized, and conjugated metabolites of chlorinated phosphorous FRs were identified, leading to the suggestion of α-oxidation as a significant metabolic pathway for these compounds.

Orbitrap™-MS provides novel insights into human metabolism of flame retardants

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Acknowledgments

The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under grant agreements PIIF-GA-2012-327232 (ADAPT project), 316665 (A-TEAM project), and 264600 (INFLAME project).

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Authors and Affiliations

  1. Division of Environmental Health and Risk Management, School of Geography, Earth and Environmental Sciences, University of Birmingham, Birmingham, B15 2TT, UK

    Mohamed Abou-Elwafa Abdallah, Gopal Pawar & Stuart Harrad

  2. Department of Analytical Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

    Mohamed Abou-Elwafa Abdallah

  3. School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK

    Jinkang Zhang, Mark R. Viant & J. Kevin Chipman

  4. Thermo Fisher Scientific, 1 Boundary Park, Hemel Hempstead, HP2 7GE, UK

    Kyle D’Silva

  5. Thermo Fisher Scientific (Bremen) GmbH, 28199, Bremen, Germany

    Maciej Bromirski

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  1. Mohamed Abou-Elwafa Abdallah
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Correspondence to Mohamed Abou-Elwafa Abdallah.

Electronic supplementary material

Further details on analytical method optimization, QA/QC measurements and structural confirmation of metabolites are provided as electronic supplementary material.

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Abdallah, M.AE., Zhang, J., Pawar, G. et al. High-resolution mass spectrometry provides novel insights into products of human metabolism of organophosphate and brominated flame retardants. Anal Bioanal Chem 407, 1871–1883 (2015). https://doi.org/10.1007/s00216-015-8466-z

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  • DOI: https://doi.org/10.1007/s00216-015-8466-z

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