Analytical methods for the determination of mixtures of bisphenols and derivatives in human and environmental exposure sources and biological fluids. A review.

Bisphenol A (BPA) is ubiquitous in humans and the environment. Its potential adverse effects through genomic and non-genomic pathways have fostered BPA replacement by bisphenol analogs that, unfortunately, exert similar adverse effects. Many of these analogs, as well as their derivatives, have already found in humans and the environment and major concerns have arisen over their low dose- and mixture-related effects. This review aims to discuss the characteristics of the main analytical methods reported so far for the determination of mixtures of bisphenol analogs and/or derivatives in human and environmental exposure sources and biological fluids. Approaches followed for removal of background contamination, sample preparation and separation and detection of mixtures of bisphenols and derivatives are critically discussed. Sample treatment is matrix-dependent and common steps include analyte isolation, removal of interferences, evaporation of the extracts and solvent reconstitution. Separation and quantification has been almost exclusively carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC-MS), in the last case prior derivatization, but LC-fluorescence detection has also found some applications. Main characteristics, advantages and drawbacks of these methods will be comparatively discussed. Although at an early stage, some approaches for the assessment of the risk to mixtures of bisphenols, mainly based on the combination of chemical target analysis and toxicity evaluation, have been already applied and they will be here presented. Current knowledge gaps hindering a reliable assessment of human and environmental risk to mixtures of bisphenols and derivatives will be outlined.