Optimization of a Method for the Determination of a Mustard Gas Biomarker in Human Blood Plasma by Liquid Chromatography–Mass Spectrometry
https://doi.org/10.35825/2587-5728-2017-1-3-7-17
EDN: yoqccd
Abstract
A method for the determination of a mustard gas biomarker (an S-hydroxyethylthioethyl adduct with albumin) in blood plasma was optimized with the use of HPLC with tandem mass-spectrometric detection. This method is based on the hydrolysis of this adduct by the proteinase K enzyme with the formation of the following stable tripeptide with cysteine, proline, and phenylalanine: S-HETECys-Pro-Phe. The detection limit of mustard gas in human blood plasma was 2 ng/ml. The approach proposed was tested in the analysis of human blood plasma samples by the standard addition technique and also within the framework of the first official biomedical test carried out by the Organization for the Prohibition of Chemical Weapons (OPCW) in 2016, and it exhibited a good accuracy, reproducibility, and specificity of determination.
About the Authors
А. V. BraunRussian Federation
Senior Researcher. Candidate of Chemical Sciences
Brigadirskii Lane 13, Moscow 105000
I. V. Rybalchenko
Russian Federation
Leading Researcher. Doctor of Chemical Sciences. Professor
Brigadirskii Lane 13, Moscow 105000
V. N. Fateenkov
Russian Federation
Chief of the Department. Candidate of Military Sciences
Brigadirskii Lane 13, Moscow 105000
М. А. Ponsov
Russian Federation
Senior Researcher. Candidate of Chemical Sciences
Brigadirskii Lane 13, Moscow 105000
Y. V. Stavitskay
Russian Federation
Researcher
Brigadirskii Lane 13, Moscow 105000
D. V. Oreshkin
Russian Federation
Researcher
Brigadirskii Lane 13, Moscow 105000
References
1. Convention on the prohibition of the development, production, stockpiling and use of chemical weapons and on their destruction. GE.92- 61926, Paris. 1993. P. 52–55 (in Russian).
2. Comment of the information department of the Russian Foreign Ministry to the reports of the Mission on the establishment of facts of the use of chemical weapons in Syria and the NGO «Human Rights Watch» / MFA of the Russian Federation, 06.05.2017. URL: http://www.mid.ru/foreign_policy/news/-/asset_publisher/cKNonkJE02Bw/content/id/2746077 (in Russian).
3. Capacio B.R., Smith J.R., Lawrence R.J., Boyd B. L., Witriol A.M., Conti M.L., Collins J.L., Sciuto A.M. Gas chromatographic-mass spectrometric analysis of sulfur mustard-plasma protein adduct: validation and use in a rat inhalation model // J. Anal. Toxicol. 2008. V. 32. P. 37–43.
4. Noort D., Benschop H.P., Black R.M. Biomonitoring of exposure to chemical warfare agents: a review // Toxicol. Appl. Pharm. 2002. V. 184. P. 116-126.
5. Barr J.R., Pierce C.L., Smith J.R., Capacio B.R., Woolfitt A.R., Solano M.I., Wooten J.V., Lemire S.W., Thomas J.D., Ash D.H., Ashley D.L. Analysis of urinary metabolites of sulfur mustard in two individuals after accidental exposure // J. Anal. Toxicol. 2008. V. 32. P. 10–16.
6. Newmark J., Langer J.M., Capacio B., Barr J., McIntosh R.G. Liquid sulfur mustard exposure // Military Med. 2007. V. 172. P. 196–198.
7. Benschop H.P., Van der Schans G.P., Noort D., Fidder A., Mars-Groenendijk R.H., de Jong L.P. Verification of exposure to sulfur mustard in two casualties of the Iran-Iraq conflict // J. Anal. Toxicol. 1997. V. 21. P. 249–251.
8. Xu H., Nie Z., Zhang Y., Li C., Yue L., Yang W., Chen J., Dong Y., Liu Q., Lin Y., Wu B., Feng, J., Lia H., Guo L., Xie J. Four sulfur mustard exposure cases: overall analysis of four types of biomarkers in clinical samples provides positive implication for early diagnosis and treatment monitoring // Toxicol. Reports. 2014. V. 1. P. 533–543.
9. Van der Schans G.P., Mars-Groenendijk R., de Jong L.P., Benschop H.P., Noort D. Standard operating procedure for immunuslotblot assay for analysis of DNA/Sulfur mustard adducts in human blood and skin // J. Anal. Toxicol. 2004. V. 28. P. 316–319.
10. Noort D., Hulst A.G., Trap H.C., de Jong L.P., Benschop H.P. Synthesis and mass spectrometric identification of the major amino acid adducts formed between sulphur mustard and haemoglobin in human blood // Arch. Toxicol. 1997. V. 71. P. 171–178.
11. Black M.R., Read W.R. Improved methodology for the detection and quantitation of urinary metabolites of sulphur mustard using gas chromatography-tandem mass spectrometry // J. Chrom. B. 1995. V. 665. P. 97–105.
12. Noort D., Fidder A., Hulst A.G., Woolfitt A.R., Ash D., Barr J.R. Retrospective detection of exposure to sulfur mustard: improvements on an assay for liquid chromatography-tandem mass spectrometry analysis of albumin/sulfur mustard adducts // J. Anal. Toxicol. 2004. V. 28. P. 333–338.
13. Pantazides B., Crow B., Garton J., QuinonesGonzales J., Blake T., Thomas J., Johnson R.A. A simplified method for quantifying sulfur mustard adducts to blood proteins by ultra-high pressure liquid chromatography-isotope dilution tandem mass spectrometry // J. Chemical Research in Toxicology. 2015. V. № 2. P. 256–261.
14. Noort D., Hulst A.G., De Jong L.P., Benschop H.P. Alkylation of human serum albumin by sulfur mustard in vitro and in vivo: mass spectrometric analysis of a cysteine adduct as a sensitive biomarker of exposure // Chem. Res. Toxic. 1999. V. 12. P. 715–721.
Review
For citations:
Braun А.V., Rybalchenko I.V., Fateenkov V.N., Ponsov М.А., Stavitskay Y.V., Oreshkin D.V. Optimization of a Method for the Determination of a Mustard Gas Biomarker in Human Blood Plasma by Liquid Chromatography–Mass Spectrometry. Journal of NBC Protection Corps. 2017;1(3):7-17. (In Russ.) https://doi.org/10.35825/2587-5728-2017-1-3-7-17. EDN: yoqccd