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

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 mu g 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 C-13(12)-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 mu g kg(-1). The detection and quantification limits ranged from 0.001 to 0.030 mu g kg(-1) and from 0.002 to 0.050 mu g 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-dela-Loire. The measured levels of BPA were found in the