Simultaneous determination of bisphenol A and its chlorinated derivatives in human plasma: Development, validation and application of a UHPLC-MS/MS method.

Bisphenol A (BPA) is a well-known ubiquitous chemical found in polycarbonate, polysulfone and epoxy resins, used in mass production for many consumer products. BPA exhibits endocrine disruptor properties that can potentially induce adverse health effects. In aquatic environments, it can react with chlorine to produce chlorinated derivatives (ClxBPAs). ClxBPAs exhibit oestrogenic activity 10 to 105 times higher than BPA itself. Assessing human exposure to endocrine disrupting chemicals is mandatory to assess health risk. Blood, as well as urine matrix, are commonly used to perform human biomonitoring. We therefore developed, fully validated and applied a method based on Ultra High Performance Liquid Chromatography couples to a Triple Quad Mass Spectrometer to determine BPA, monochlorobisphenol A (MCBPA), dichlorobisphenol A (DCBPA), trichlorobisphenol A (TCBPA) and tetrachlorobisphenol A (TTCBPA) in human blood plasma. The European Medicines Agency guidelines for bioanalytical method validation have been applied. Precision and trueness of the method were <15% at medium and high levels of quality control and <20% at the limits of quantification (LOQs). The LOQs were settled at 0.1 ng/mL for BPA, 0.02 ng/mL for TTCBPA and 0.005 ng/mL for MCBPA, DCBPA, and TCBPA. The analytical method was applied to ten patients suffering from end stage renal disease. BPA was quantified in all ten patients while MCBPA, DCBPA and TTCBPA were determined in three and TCBPA in four. In conclusion, we have successfully developed a highly sensitive method to determine BPA and ClxBPAs in human plasma. Thanks to this method, for the first time, we could demonstrate ClxBPAs occurrence in human blood.