Analytical and Bioanalytical Chemistry, volume 413, issue 28, pages 6973-6985
Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry
Vokuev M F
1
,
Baygildiev Т М
1
,
Plyushchenko I V
1
,
Ikhalaynen Y A
1
,
Ogorodnikov R L
1
,
Solontsov I K
1
,
Braun А V
1, 2
,
Savelieva E I
3
,
Rуbalchenko I V
1, 2
,
Rodin I A
1, 4
2
Laboratory for the Chemical and Analytical Control of the Military Research Centre, Moscow, Russia
|
Publication type: Journal Article
Publication date: 2021-09-21
Quartile SCImago
Q2
Quartile WOS
Q1
Impact factor: 4.3
ISSN: 16182642, 16182650
Biochemistry
Analytical Chemistry
Abstract
Chemical warfare agents continue to pose a real threat to humanity, despite their prohibition under the Chemical Weapons Convention. Sarin is one of the most toxic and lethal representatives of nerve agents. The methodology for the targeted analysis of known sarin metabolites has reached great heights, but little attention has been paid to the untargeted analysis of biological samples of victims exposed to this deadly poisonous substance. At present, the development of computational and statistical methods of analysis offers great opportunities for finding new metabolites or understanding the mechanisms of action or effect of toxic substances on the organism. This study presents the targeted LC-MS/MS determination of methylphosphonic acid and isopropyl methylphosphonic acid in the urine of rats exposed to a non-lethal dose of sarin, as well as the untarget urine analysis by LC-HRMS. Targeted analysis of polar acidic sarin metabolites was performed on a mixed-mode reversed-phase anion-exchange column, and untargeted analysis on a conventional reversed-phase C18 column. Isopropyl methylphosphonic acid was detected and quantified within 5 days after subcutaneous injection of sarin at a dose of 1/4 LD50. A combination of generalized additive mixed models and dose-response analysis with database searches using accurate mass of precursor ions and corresponding MS/MS spectra enabled us to propose new six potential biomarkers of biological response to exposure. The results confirm the well-known fact that sarin poisoning has a significant impact on the victims’ metabolome, with inhibition of acetylcholinesterase being just the first step and trigger of the complex toxicodynamic response.
Citations by journals
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1
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TrAC - Trends in Analytical Chemistry
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TrAC - Trends in Analytical Chemistry
1 publication, 33.33%
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Journal of Chromatography A
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Journal of Chromatography A
1 publication, 33.33%
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1
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Citations by publishers
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1
2
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Elsevier
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Elsevier
2 publications, 66.67%
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1
2
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Vokuev M. F. et al. Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry // Analytical and Bioanalytical Chemistry. 2021. Vol. 413. No. 28. pp. 6973-6985.
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Vokuev M. F., Baygildiev Т. М., Plyushchenko I. V., Ikhalaynen Y. A., Ogorodnikov R. L., Solontsov I. K., Braun А. V., Savelieva E. I., Rуbalchenko I. V., Rodin I. A. Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry // Analytical and Bioanalytical Chemistry. 2021. Vol. 413. No. 28. pp. 6973-6985.
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TY - JOUR
DO - 10.1007/s00216-021-03655-3
UR - https://doi.org/10.1007%2Fs00216-021-03655-3
TI - Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry
T2 - Analytical and Bioanalytical Chemistry
AU - Vokuev, M F
AU - Baygildiev, Т М
AU - Plyushchenko, I V
AU - Ikhalaynen, Y A
AU - Ogorodnikov, R L
AU - Solontsov, I K
AU - Savelieva, E I
AU - Rуbalchenko, I V
AU - Rodin, I A
AU - Braun, А V
PY - 2021
DA - 2021/09/21 00:00:00
PB - Springer Nature
SP - 6973-6985
IS - 28
VL - 413
SN - 1618-2642
SN - 1618-2650
ER -
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@article{2021_Vokuev,
author = {M F Vokuev and Т М Baygildiev and I V Plyushchenko and Y A Ikhalaynen and R L Ogorodnikov and I K Solontsov and E I Savelieva and I V Rуbalchenko and I A Rodin and А V Braun},
title = {Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry},
journal = {Analytical and Bioanalytical Chemistry},
year = {2021},
volume = {413},
publisher = {Springer Nature},
month = {sep},
url = {https://doi.org/10.1007%2Fs00216-021-03655-3},
number = {28},
pages = {6973--6985},
doi = {10.1007/s00216-021-03655-3}
}
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Vokuev, M. F., et al. “Untargeted and targeted analysis of sarin poisoning biomarkers in rat urine by liquid chromatography and tandem mass spectrometry.” Analytical and Bioanalytical Chemistry, vol. 413, no. 28, Sep. 2021, pp. 6973-6985. https://doi.org/10.1007%2Fs00216-021-03655-3.
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