Determination of metabolites of the epoxy resin component bisphenol A diglycidyl ether (BADGE) in human urine using gas chromatography-tandem mass spectrometry

Bisphenol A diglycidyl ether (BADGE) is used as an epoxy resin component in numerous applications in industry and the consumer sector. Its use for inner coatings of food and beverage cans poses a source for BADGE exposure in the general population since migration of BADGE or its derivatives from coatings into food items takes place. The compound is currently under assessment as an endocrine disruptor and a potent skin sensitiser. Nevertheless, a reliable biomarker for estimating BADGE intake by humans has yet to be identified. The objective of the study was to develop and validate a human biomonitoring method that is suitable to detect BADGE exposure down to the concentration range of environmental background exposure. The analytical method presented here enables a sensitive and specific determination of the BADGE metabolites BAGE*H 2 O, BADGE*H 2 O*AcOH, and BADGE*2H 2 O in urine by gas chromatography-tandem mass spectrometry (GC–MS/MS). Following enzymatic hydrolysis and liquid–liquid extraction of the samples, three derivatisation steps are performed to enhance the volatility of the comparatively polar analytes. Metabolite concentrations are subsequently determined by GC–MS/MS using external calibration and isotope-labelled internal standardisation. Validation of the method yielded limits of quantification between 0.07 and 0.10 μg/L, with day-to-day precision between 4.4 and 15.2% and relative recoveries between 81 and 114% depending on the particular analyte. An analysis of n = 40 spot urine samples from the general population showed quantifiable analyte concentrations in isolated samples. Compared to the most commonly used biomarker BADGE*2H 2 O, the downstream metabolite BADGE*H 2 O*AcOH could be a promising alternative as it is less susceptible to contamination from external sources.