Simultaneous quantification of bisphenol A, its glucuronide metabolite and commercial alternatives by LC-MS/MS for in vitro skin absorption evaluation

Bisphenol A (BPA) is the most used color developer in thermal paper products such as cashiers’ receipts, followed by Bisphenol S (BPS), Wincon 8 (D-8), and Pergafast 201 (PF201). These chemicals can migrate from the paper onto the skin and possibly be absorbed and metabolized. Until now, D-8 and PF201 have not been analyzed in biological matrices, nor has a method been developed to simultaneously quantify them, even though they are often found as mixtures. Our aim was to develop and validate a method to quantify BPA, its glucuronide metabolite (BPA-G), BPS, D-8, and PF201 in in vitro skin absorption samples. After solid-phase extraction and reversed-phase chromatography, we quantified the substances in saline that had been in contact with human dermis for 24 h using a triple-quadrupole mass detector equipped with an electrospray ionization source. We assessed the method in three in vitro skin absorption assays using ex vivo human skin from one skin donor per test substance. The quantification ranges of our method were 0.2–200 μg/L for BPA and 0.2–20 μg/L for BPA-G, BPS, D-8, and PF201. Accuracies were within ±8% of nominal concentrations. Intra-day and total precisions (%RSD) were <10% for all analytes, except for BPA in low-concentration quality control solutions (low QCs) (12.2% and 15.5%, respectively). Overall, the process efficiency was 100–113% for all analytes, except BPS low and high QCs (80% and 71%, respectively) and BPA low QCs (134%). The absorbed dose ranged from 0.02% to 49% depending on the test substance, and was not determinable for PF201. This is the first analytical method to quantify simultaneously BPA, BPA-G, and BPA alternatives in saline from in vitro skin absorption samples.