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Verification of SM Exposure in Biological Samples

  • Dirk Steinritz
  • Horst ThiermannEmail author
Chapter

Abstract

Sulfur mustard (SM) is a potent vesicant chemical warfare agent. Use of such agents is considered as “crossing a red line”. Exposure to SM via inhalational, cutaneous and ocular route can result in a systemic uptake causing the formation of specific biomarkers that can be of use for verification. Comprehensive methods for a free of doubt verification in biological samples do exist that detect either remaining pure SM in the circulation and tissues, or rely on biomarkers resulting from SM hydrolysis, SM biotransformation products, SM protein adduct or SM DNA adduct formation.

This chapter provides an overview about existing biomarkers that indicate a SM exposure and analytical methods for their detection with special focus on the respective toxicokinetics. Intact SM in urine or blood can be analyzed by GC- or LC-MS methods in a short time frame after exposure. Specific ß-lyase metabolites and non-specific TDG have also been successfully determined by GC- or LC-MS methods. Several specific protein adducts with SM do occur, including albumin and hemoglobin, and are frequently used for verification purposes. Finally, SM-DNA adducts can be visualized with immunohistochemical methods or with evidentiary LC-MS based methods.

Keywords

Sulfur Mustard Verification Mass spectrometry Biotransformation products Protein adducts DNA adducts 

Notes

Glossary

ß-lyase metabolites

Specific SM-biotransformation products that can be detected in urine after sulfur mustard exposure

Biological samples

(Non-environmental) samples collected from organisms such as blood, urine and other tissues

Biomarker

Specific analyte that is measured to prove an exposure

Biomedical verification

Use of analytical methods (typically mass spectrometry based methods) for the assessment of biomarkers in order to prove the exposure towards SM

Biotransformation products

Enzymatical, chemical modification of compounds by an organism

DNA-adducts (N7-HETEG, Bis-G, N3-HETEA, O6-HETEG)

Sulfur mustard induced covalent modification of DNA-bases. N7-HETEG is the alkylation of guanine at the N7 position, Bis-G represents the a DNA crosslink between two guanines at the N7 positions, N3-HETEA is the alkylation of adenine at the N3 position and O6-HETEG represents alkylation of guanine at O6 residues

GC-MS

Gas chromatography–mass spectrometry uses a capillary column for sample separation and mass spectrometry for analysis

Half-life

Time after that the concentration of a compound will drop to 50 % of the initial concentration

Hydrolysis

Cleavage of chemical bounds in aquoues surroundings

Immunohistochemistry

Visualization of antigens in tissue by the use of antibodies

LC-MS

Liquid chromatography–mass spectrometry is an analytical technique that combines liquid chromatography for separation and mass spectrometry for analysis

MALDI-TOF

Matrix-assisted laser desorption/ionization (MALDI) and time-of-flight mass spectrometer can be used for the rapid identification of proteins and their modifications

Sulfur mustard

Vesicant chemical warfare agent, first used in World War I.

Sulfur mustard adduct formation

Covalent modification of biological targets by sulfur mustard.

TDG

Thiodiglycol is a hydrolysis product of sulfur mustard. In contrast to ß-lyase metabolites TDG is also present in the urine of unexposed persons.

Toxicokinetic

Fate of a compound after entering the organism (e.g. distribution, hydrolysis, metabolism, excretion)

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Bundeswehr Institute of Pharmacology and ToxicologyMunichGermany

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