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.
Anal Chim Acta. 2015 Sep 24; 894:54-64.AC

Abstract

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

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Authors+Show Affiliations

Zhang Y

Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China; Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China.

Wang Q

Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China.

Cheng J

Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China.

Zhang J

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang, China.

Xu J

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang, China.

Ren Y

Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang, China. Electronic address: renyiping@263.net.

MeSH

AcetylcysteineAcrylamideAnimalsBiomarkersChemistry Techniques, AnalyticalChromatography, High Pressure LiquidDietFemaleHumansIsotopesMaleRatsRats, Sprague-DawleyTandem Mass SpectrometryToxicokineticsYoung Adult

Pub Type(s)

Evaluation Study

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26423628

Citation

Zhang, Yu, et al. "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." Analytica Chimica Acta, vol. 894, 2015, pp. 54-64.

Zhang Y, Wang Q, Cheng J, et al. 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. Anal Chim Acta. 2015;894:54-64.

Zhang, Y., Wang, Q., Cheng, J., Zhang, J., Xu, J., & Ren, Y. (2015). 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. Analytica Chimica Acta, 894, 54-64. https://doi.org/10.1016/j.aca.2015.08.033

Zhang Y, et al. 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. Anal Chim Acta. 2015 Sep 24;894:54-64. PubMed PMID: 26423628.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - 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. AU - Zhang,Yu, AU - Wang,Qiao, AU - Cheng,Jun, AU - Zhang,Jingshun, AU - Xu,Jiaojiao, AU - Ren,Yiping, Y1 - 2015/08/25/ PY - 2015/07/28/received PY - 2015/08/16/accepted PY - 2015/10/2/entrez PY - 2015/10/2/pubmed PY - 2016/4/14/medline KW - Acrylamide KW - Glycidamide KW - Internal exposure KW - Mercapturic acid metabolites KW - Toxicokinetics KW - Urinary biomarkers SP - 54 EP - 64 JF - Analytica chimica acta JO - Anal Chim Acta VL - 894 N2 - Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1-0.3 ng/mL and 0.4-1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% and 92.2%-108.9%, respectively. Acceptable within-laboratory reproducibility (RSD<7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive profiling of toxicokinetics and daily internal exposure evaluations of acrylamide in vivo. SN - 1873-4324 UR - https://www.unboundmedicine.com/medline/citation/26423628/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_ DB - PRIME DP - Unbound Medicine ER -

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