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利用串聯式液相層析質譜法同時分析丙烯醯胺職業暴露工人尿液代謝物

Simultaneous Determination of Urinary Mercapturic Acids for Acrylamide Exposed Workers by LC-MS/MS

摘要


Acrylamide (AA) has been widely used in industry to produce flocculants and grouting agents as well as in biological laboratories for the preparation of polyacrylamide gels for electrophoresis. It is classified as a probable human carcinogen (Group 2A) by the IARC. Workers are at risk of AA exposures. AA can be metabolized into AA N-acetyl-S-(propionamide)-cysteine (AAMA) and of Glycidamide (GA) N-acetyl-S-(carbamoyl-2-hydroxyethyl)-cysteine (GAMA2) and N-acetyl-S-(3- amino-2-hydroxy-3-oxopropyl)-cysteine (GAMA3). Analysis of these mercapturic acids (MAs) can serve as biomarkers for AA exposures and illustrate the metabolism of AA in human. In our study, a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously analyze urinary AAMA, GAMA2 and GAMA3 for the AA-exposed workers. Fifty six AA-exposed workers and 36 controls were recruited and provided a pair of pre- and post-shift urine samples for this study. The results showed the limit of detection (LOD) values were <10 ng/mL (GAMA2) , 20 ng/mL (GAMA3) and 5 ng/mL (AAMA) in urine and the detection rate was 34%, 38% and 92% for GAMA2, GAMA3 and AAMA, respectively. The geometric mean (range) level of GAMA2, GAMA3 and AAMA in the whole collective (n=100) was 38.2 (8.1-343) (μg/g creatinine), 94.9(10.8-1754.6) (μg/g creatinine) and 516.7 (4.7-115843) (μg/g creatinine), respectively. There was a significantly positive correlation between naturally log-transformed concentrations of AAMA and naturally log-transformed GAMA2 and GAMA3 (Pearson correlation: r=0.695, p<0.001). Besides, the pre- and post-shift urinary AAMA concentrations for the AA-exposed workers were higher than those for the controls. These results suggest that AAMA can serve as a sensitive, specific, non-invasive, and easily accessible biomarker for AA exposures.

並列摘要


Acrylamide (AA) has been widely used in industry to produce flocculants and grouting agents as well as in biological laboratories for the preparation of polyacrylamide gels for electrophoresis. It is classified as a probable human carcinogen (Group 2A) by the IARC. Workers are at risk of AA exposures. AA can be metabolized into AA N-acetyl-S-(propionamide)-cysteine (AAMA) and of Glycidamide (GA) N-acetyl-S-(carbamoyl-2-hydroxyethyl)-cysteine (GAMA2) and N-acetyl-S-(3- amino-2-hydroxy-3-oxopropyl)-cysteine (GAMA3). Analysis of these mercapturic acids (MAs) can serve as biomarkers for AA exposures and illustrate the metabolism of AA in human. In our study, a liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously analyze urinary AAMA, GAMA2 and GAMA3 for the AA-exposed workers. Fifty six AA-exposed workers and 36 controls were recruited and provided a pair of pre- and post-shift urine samples for this study. The results showed the limit of detection (LOD) values were <10 ng/mL (GAMA2) , 20 ng/mL (GAMA3) and 5 ng/mL (AAMA) in urine and the detection rate was 34%, 38% and 92% for GAMA2, GAMA3 and AAMA, respectively. The geometric mean (range) level of GAMA2, GAMA3 and AAMA in the whole collective (n=100) was 38.2 (8.1-343) (μg/g creatinine), 94.9(10.8-1754.6) (μg/g creatinine) and 516.7 (4.7-115843) (μg/g creatinine), respectively. There was a significantly positive correlation between naturally log-transformed concentrations of AAMA and naturally log-transformed GAMA2 and GAMA3 (Pearson correlation: r=0.695, p<0.001). Besides, the pre- and post-shift urinary AAMA concentrations for the AA-exposed workers were higher than those for the controls. These results suggest that AAMA can serve as a sensitive, specific, non-invasive, and easily accessible biomarker for AA exposures.

參考文獻


(2003).Standards of Permissible Exposure Limits of Airborne Hazardous Substances in Workplace Lao. An-3-Tzu No. 0920073294.(Labor Commlssion, Ministry of the Interior on Dec 31).
Bjellaas T,Janak K,Lundanes E,Kronberg L,Becher G.(2005).Determination and quantification of urinary metabolites after dietary exposure to acrylamide.Xenobiotica.35,1003-1018.
Bjellaas T,Stolen-LH,Haugen M(2008).Urinary acrylamide metabolites as biomarkers for short-term dietary exposure to acrylamide.(Food and Chemical Toxicology In Press, Corrected Proof).
Boettcher MI,Bolt HM,Drexler H,Angerer J.(2006).Excretion of mercap-tune acids of acrylamide and glycidamide in human urine after single oral administration of deuteriumlabelled acrylamide.Arch Toxicol.80(2),55-61.
Bull PJ,Brooke RE,Cocker J,Jones K(2005).An occupational hygiene investigation of exposure to acrylamide and the role for urinary S-Carboxyethyl-Cysteine (CEC) as a biological marker.Ann Occup Hyg.49,683-690.

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