Development and validation of an LC-MS/MS method for the simultaneous determination of bisphenol A and its chlorinated derivatives in adipose tissue

Abstract

Bisphenol A (BPA) and its chlorinated derivatives (Clx-BPA) are environmental pollutants exhibiting endocrine-disrupting (ED) properties suspected to be involved in the pathogenesis of hormone-dependent cancers, such as breast and prostate cancers. Due to their lipophilic properties, they may accumulate in adipose tissue which could therefore be a suitable matrix to assess long-term exposure to these compounds and relationships with the tumorigenesis of these cancers. An LC-MS/MS assay for the determination of BPA and Clx-BPA in adipose tissue samples was developed and fully validated according to current bioanalytical validation guidelines. Ionization was achieved using an electrospray source operating in the negative mode and quantification of target analytes was obtained in the multiple reaction monitoring mode. Both standard and quality control (QC) samples were prepared in blank adipose tissue samples. Linearity was demonstrated over the ranges 0.125 to 8.000 and 0.0125-0.8000 ng/mL for BPA and Clx-BPA, respectively. Accuracy and precision were demonstrated over the whole concentration range: intra and inter-day bias values were in the 85-114% range and imprecision of the method did not exceed 14%. Lower limits of quantification were validated using QCs at 0.1250 and 0.0125 ng/mL for BPA and Clx-BPA, respectively. Internal standard-corrected matrix effects were comparable in breast and prostate adipose tissues, demonstrating that this method could be used to reliably assay BPA and Clx-BPA in both tissues. The method was sensitive enough to determine BPA and Clx-BPA in breast adipose tissue obtained from women undergoing breast surgery, enabling identification of different patterns of exposure to these ED chemicals. The method enables the reliable quantification of BPA and Clx-BPA in adipose tissue and could be used to assess long-term exposure to these compounds and potential associations with hormone-dependent cancers.

Keywords: Adipose tissue; Bisphenol A and its chlorinated derivatives; Breast; Endocrine disruptors; Hormone-dependent cancer; Prostate.