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Simultaneous determination of 14 urinary biomarkers of exposure to organophosphate flame retardants and plasticizers by LC-MS/MS

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Abstract

Organophosphate flame retardants and plasticizers (PFRs) are a group of chemicals widely added to consumer products. PFRs are quickly metabolized in the human body into two types of metabolites, (1) dialkyl and diaryl phosphate esters (DAPs), such as diphenyl phosphate (DPHP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP); and (2) hydroxylated PFRs (HO-PFRs), such as 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and 2-hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP). Existing analytical methods usually focus on DAPs; therefore, human biomonitoring data on HO-PFRs remain scarce. In this study, an analytical procedure was developed for the simultaneous quantification of multiple PFR metabolites in human urine, covering eight DAPs and six HO-PFRs. Sample preparation was optimized to include all target compounds using Bond-Elut C18 solid-phase extraction cartridges, followed by instrumental analysis based on liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS). Method performance was validated according to established guidelines and satisfactory results were obtained for all metabolites in terms of recovery, linearity, limits of quantification, precision, and accuracy. Recoveries ranged from 87 to 112%. Method detection limits from 0.002 ng/mL for 2-ethyl-5-hydroxyhexyl diphenyl phosphate (5-HO-EHDPHP) to 0.66 ng/mL for 4-hydroxyphenyl phenyl phosphate (4-HO-DPHP). Seven PFR metabolites were frequently detected in a small biomonitoring study (n = 14), among them bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), di-n-butyl phosphate (DNBP), 5-HO-EHDPHP, and BBOEHEP. Highest mean concentrations were found for DPHP, 2-ethylhexyl phenyl phosphate (EHPHP), and BCIPHIPP, while 4-HO-DPHP, 5-HO-EHDPHP, and EHPHP were detected in urine for the first time. Overall, the obtained results demonstrate that the developed method can be used for the simultaneous determination of 14 urinary biomarkers of exposure to PFRs.

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Acknowledgments

Michiel Bastiaensen acknowledges the partial funding of his Ph.D. through the Flemish Environment and Health Study financed by the Ministry of the Flemish Community (Department of Economics, Science and Innovation; Flemish Agency for Care and Health; and Department of Environment, Nature and Energy). Research leading to these results has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement #316665 (A-TEAM project). Frederic Been would like to thank the Research Foundation—Flanders (FWO) for his postdoctoral grant (12Y8518N).

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Correspondence to Michiel Bastiaensen or Adrian Covaci.

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Bastiaensen, M., Xu, F., Been, F. et al. Simultaneous determination of 14 urinary biomarkers of exposure to organophosphate flame retardants and plasticizers by LC-MS/MS. Anal Bioanal Chem 410, 7871–7880 (2018). https://doi.org/10.1007/s00216-018-1402-2

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  • DOI: https://doi.org/10.1007/s00216-018-1402-2

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