Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry.

摘要: Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most studies have focused on measurement two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, comprehensive profile urinary cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method simultaneous determination all four mercapturic adducts its primary metabolite glycidamide under electroscopy ionization negative (ESI-) mode present study. The limit detection (LOD) quantification (LOQ) analytes ranged 0.1-0.3 ng/mL 0.4-1.0 ng/mL, respectively. recovery rates with low, intermediate high spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% 92.2%-108.9%, Acceptable within-laboratory reproducibility (RSD<7.0%) substantially supported use current robust analysis. Rapid pretreatment procedures short run time (8 min per sample) ensured good efficiency metabolism profiling, indicating a wide application investigating internal Our proposed UHPLC-MS/MS was successfully applied to toxicokinetic study rats. Meanwhile, results human urine analysis indicated that N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear rodents, more than sum GAMA N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). AAMA-sul may alternatively become specific biomarker humans. Current provides substantial methodology support profiling toxicokinetics daily evaluations vivo.