Glucuronide and Sulfate Conjugates of Bisphenol A: Chemical Synthesis and Correlation Between Their Urinary Levels and Plasma Bisphenol A Content in Voluntary Human Donors

Bisphenol A (BPA) glucuronide and sulfate conjugates are major products of Phase II metabolism of BPA in humans. In the past, their determination in body fluids usually involves tedious enzymatic hydrolysis and multiresidual analysis. The recent availability of authentic standards of these conjugates enables our better understand of the human metabolism of BPA and the distribution of their metabolites in body fluids. In this work, we report the chemical synthesis and purification of BPA mono- and di-glucuronide and BPA mono- and di-sulfate. Their levels, as well as that of BPA, in 140 paired human plasma and urine samples collected randomly from voluntary donors in Hong Kong SAR, China, were determined by solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). BPA was found in more than 135 human plasma and urine samples. Its Phase II metabolites, ranging from N.D. to 36.7 A mu g g(-1)-creatinine, also were detected in 139 of the 140 urine samples. Good correlation (r = 0.911) between molar concentration of BPA in the plasma and that of "total urinary BPA" (i.e., ln [(BPA + a BPA phase II conjugate)(molar concentration)]) was observed. Direct quantification of Phase II metabolites of BPA in human urine can be a useful assessment tool for population exposure to this potent endocrine disrupting chemical.Research Grants Council of the Hong Kong Special Administrative Region, China [CityU 160513]; program of 2012 "Great Concentration Foreign Experts" - State Administration of Foreign Experts Affairs, the People's Republic of China [GDW20123200120]; Einstein Professor Program of the Chinese Academy of Sciences; Canada Research Chair program; Visiting Distinguished Professorship in the Department of Biology and Chemistry; State Key Laboratory in Marine Pollution, City University of Hong KongSCI(E)ARTICLE3410-4207