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Determination of bisphenol A and related substitutes/analogues in human breast milk using gas chromatography-tandem mass spectrometry

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Abstract

Bisphenol A (BPA) is an industrial chemical widely used in the production of polycarbonate and epoxy resins. Identified as an endocrine-disrupting chemical (EDC), BPA is a matter of existing or ongoing restrictive regulations and then is increasingly being replaced by other analogues used as BPA’s substitutes. Human biomonitoring studies focusing on both BPA and emerging related analogues consequently appear as a requirement either for documenting the efficiency of regulatory actions toward BPA and for fuelling incoming risk assessment studies toward BPA’s substitutes. In particular, the increasing concern about the late effects consecutive to early exposures naturally identify human breast milk as a target biological matrix of interest for priority exposure assessment focused on critical sub-populations such as pregnant women, fetuses, and/or newborns. In this context, an accurate and sensitive analytical method based on gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) was developed for the quantification of 18 “BPA-like” compounds in breast milk samples at trace levels (<0.05 μg kg−1). The method includes a preliminary protein precipitation step followed by two successive solid-phase extraction (SPE) stages. Quantification of the targeted compounds was achieved according to the isotopic dilution method using 13C12-BPA as internal standard. The method was validated according to current EU guidelines and criteria. Linearity (R 2) was better than 0.99 for each molecule within the concentration range 0–5 μg kg−1. The detection and quantification limits ranged from 0.001 to 0.030 μg kg−1 and from 0.002 to 0.050 μg kg−1, respectively. The analytical method was successfully applied to the first set of human breast milk samples (n = 30) originating from French women in the Region Pays-de-la-Loire. The measured levels of BPA were found in the <LOQ–1.16 μg kg−1 range. BPS was detected in only one sample at 0.23 μg kg−1, while the other targeted molecules were not detected. The proposed methodology then appeared suitable for the further monitoring of a potential decrease of BPA levels and an increase of other BPA analogue levels as reflective of the expected incoming trend in terms of human exposure.

Analytical strategy for the determination of bisphenol compounds in human breast milk samples

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Acknowledgments

The authors are first of all very grateful to all volunteer women included in the present study from which the analyzed breast milk samples were collected. They thank the Region Pays-de-Loire, the Fond Européen de Développement Economique et Régional (FEDER, Grant 38395, Project 6226 « Lactacol »), and the Agence Nationale de la Recherche (ANR-13-CESA-0012-01 “Newplast”) for funding support. They thank the Clinical Investigation Center (CIC) from the Nantes University Hospital and also Hélène Billard (INRA PHAN) for having collected the samples.

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Deceuninck, Y., Bichon, E., Marchand, P. et al. Determination of bisphenol A and related substitutes/analogues in human breast milk using gas chromatography-tandem mass spectrometry. Anal Bioanal Chem 407, 2485–2497 (2015). https://doi.org/10.1007/s00216-015-8469-9

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