Analysis of bisphenol A diglycidyl ether (BADGE) and its hydrolytic metabolites in biological specimens by high-performance liquid chromatography and tandem mass spectrometry

Due to its cytotoxicity, genotoxicity, and adipogenicity observed in in vitro studies, bisphenol A diglycidyl ether (BADGE) may pose a health risk to humans. Quantifying BADGE exposure is an essential step to assess potential health risks associated with this ubiquitous compound widely used in certain plastic products. Due to the lack of endogenous sources for BADGE, bio-monitoring of BADGE and/or its hydrolytic metabolites (BADGE·H2O and BADGE·2H2O) can be a useful means to measure exposure. In this study, we developed a highly specific and sensitive method to measure BADGE, BADGE·H2O and BADGE·2H2O in plasma and urine, using a fast liquid–liquid extraction technique followed by a high-performance liquid chromatography and positive electrospray tandem mass spectrometry (LC–ESI-MS/MS) method. The method can quantify BADGE, BADGE·H2O and BADGE·2H2O with lower limits of quantification (LLOQ) of 0.05, 0.05 and 0.2ng/ml, respectively. The percentage deviation of mean calculated concentrations from target concentrations was within 20%, variations across repeated analyses were within 15%, and mean extraction recovery was higher than 51.4% for all the three analytes in both plasma and urine matrices. The method has been applied to venous blood samples, cord blood samples, and urine samples collected from 9 to 14 adult volunteers. Results showed that concentrations of BADGE were lower than LLOQ in all of these samples except one urine sample. Low levels of BADGE·H2O from 0.108 to 0.222ng/ml were observed in four venous blood samples and one urine sample (0.187ng/ml). In contrast, concentrations of BADGE·2H2O were higher than LLOQ, varying from 0.660 to 303.593ng/ml, in all the 10 venous blood samples and 1 cord blood sample (0.592ng/ml) and two urine samples (0.200 and 0.306ng/ml). The results suggest that bio-monitoring of blood and urine for BADGE exposure should focus on the hydrolysis derivatives of BADGE, mainly in the form of BADGE·2H2O.