First insights into the biotransformation of DBSP, a novel BPS derivative: Implications for biomonitoring and toxicokinetic investigations

Hydroxylated, glucuronide and sulfate metabolites were firstly identified in vitro . • A sensitive LC-MS/MS method was established for metabolite Semi-quantification. • Recombinant human UGT/SULT isoforms mediating DBSP metabolism were identified. • DBSP shows higher unconjugated forms and longer elimination in rat plasma than BPS. • Provide insights into the biomonitoring and toxicological assessment of DBSP. The widespread use of structural analogs to replace the endocrine-disrupting chemicals bisphenol A (BPA) and bisphenol S (BPS) has become a growing concern for both the environment and human health. As a novel BPS derivative, 2,4-bis(phenylsulfonyl)phenol (DBSP) has been frequently detected in environmental samples and human biological matrices; however, the biotransformation and toxicokinetic behavior of DBSP remain uncharacterized. To address these gaps, liquid chromatography coupled with high-resolution mass spectrometry (HRMS) was used in this study to identify DBSP metabolites from human liver microsomes/cytosolic fractions in vitro . For the first time, oxidative metabolites, as well as glucuronide and sulfate conjugates of DBSP, were identified, and a corresponding LC–MS/MS semiquantitative method was established. Further phenotyping assays using recombinant human UGT and SULT isoforms revealed that UGT1A3, UGT1A8, UGT1A9 and UGT1A1 exhibited high glucuronidation activity toward DBSP, while SULT1E1, SULT1A1, and SULT1B1 played major roles in DBSP sulfation. Pharmacokinetic analysis in rats after a single oral dose (100 μg/kg) further underscores the importance of phase II conjugation in DBSP metabolism. Compared with that of BPS, the proportion of free forms of DBSP in plasma was greater (77.0 ± 6.2%), and its elimination half-life (10.7 h) was longer, suggesting potential toxicological risk. These findings provide a critical foundation for future biomonitoring and toxicological assessments of DBSP. Download: Download high-res image (136KB) Download: Download full-size image