Ammonium hydroxide enhancing electrospray response and boosting sensitivity of bisphenol A and its analogs

As one of the most important analytical techniques for accurate quantification of bisphenol compounds, liquid chromatography coupled to online electrospray ionization (ESI) tandem mass spectrometry exhibits relative weak ESI response in negative mode, which greatly reduces their sensitivity and limits their detection at trace levels, especially in complex samples such as blood. Based on the facilitated deprotonation of bisphenol molecule under alkaline condition, post-column injection of ammonium hydroxide (NH₃·H₂O) to mass spectrometer was explored to enhance the ionization efficiency of BPA and its eight analogs and improve their analytical sensitivity. Parameters effecting response intensity and stability were investigated, including mass concentration and flow rate of NH₃·H₂O. Under the optimal conditions with the addition of 2% (w/w) of NH₃·H₂O at 4 μL min^-1, the instrument detection limits for bisphenol compounds were greatly lowered to 0.001-0.04 ng mL^-1, which were 2-28.6 times lower than the result obtained without injecting NH₃·H₂O, except TBBPA (0.03 ng mL^-1 in either case). The relative standard deviations (RSDs) for instrument repeatability of BPA and its analogs at three different concentration levels were in a range of 1.2-20%. Furthermore, a decreased matrix effects (90-111%) for bisphenols (except TBBPA) analysis in serum extracts were found compared with the result obtained without NH₃·H₂O injection (43-111%). The results demonstrated that the improved instrumental method coupled with suitable pretreatment techniques is more feasible to analyze bisphenol compounds in complex bio-samples.