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Metabolite identification and profile of endosulfan sulfate in three human liver preparations using liquid chromatography-high resolution mass spectrometry.
- Source :
-
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2020 Mar 01; Vol. 1140, pp. 121996. Date of Electronic Publication: 2020 Jan 28. - Publication Year :
- 2020
-
Abstract
- In this study, we performed the metabolism of endosulfan sulfate in human liver preparations (human liver microsomes, S9 fractions and hepatocytes) to identify new metabolites using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Endosulfan sulfate is a major oxidized metabolite of the organochlorine insecticide endosulfan, and it exhibits a similar toxicity to endosulfan. Six metabolites, including 5 novel metabolites of endosulfan sulfate, were identified in the three different human liver reaction mixtures and metabolic pathways of endosulfan sulfate were proposed. The phase I metabolites M1 and M2 were observed in human liver microsomes, S9 fractions and hepatocytes. M1 was suggested to be an endosulfan diol monosulfate and M2 was identified as (1,4,5,6,7,7-hexachloro-3-formylbicyclo[2,2,1]hept-5-en-2-yl)methyl hydrogen sulfate through the interpretation of the HRMS spectrum. The phase II metabolite M3 was produced as an endosulfan sulfate-GSH conjugate in those three liver preparations and transformed to M5 (dipeptide) in S9 fractions and hepatocytes. M3 was the most predominant metabolite identified in the three liver preparations. M4 was only detected in microsomes as an M2-GSH conjugate and was metabolized to M6 (monopeptide) in hepatocytes. These results are different from the metabolic pathway of endosulfan and suggest the possible detoxification metabolic reaction of endosulfan sulfate in living organisms.<br />Competing Interests: Declaration of Competing Interest None.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Chromatography, High Pressure Liquid
Endosulfan analysis
Endosulfan metabolism
Hepatocytes metabolism
Humans
Liver metabolism
Metabolome physiology
Microsomes, Liver metabolism
Oxidation-Reduction
Sulfuric Acid Esters analysis
Sulfuric Acid Esters metabolism
Tandem Mass Spectrometry
Endosulfan analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1873-376X
- Volume :
- 1140
- Database :
- MEDLINE
- Journal :
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32014661
- Full Text :
- https://doi.org/10.1016/j.jchromb.2020.121996