Abstract
A procedure for determination of the lewisite metabolite 2-chlorovinylarsonous acid (CVAA) in biomedical samples, involving derivatization of the latter with propane-1,3-dithiol and head-space solid-phase microextraction of the derivative on a 100-μm PDMS fiber followed by GC-MS, was applied for the first time to analysis ofin vivosamples. The detection limits of CVAA in urine, plasma and red blood cells were 0.1, 1.0 and 10 ng/ml, respectively. Upon exposure to lewisite at a dose of 1.6 mg/kg, CVAA could be detected in rat urine for about three months. Study of the effect of a single injection of the antidote unithiol on the CVAA excretion profile revealed more active CVAA excretion during the first two days after the injection, compared to that observed in the absence of antidotal therapy.
Highlights
Identification and quantification of chemical warfare agents (CWAs) and their metabolic products in biomedical samples is an essential component of the complex measures applied to verification of the implementation of the Chemical Weapons Convention (CWC) [4]
Vilensky et al [11] suggested that chlorovinylarsonic acid (CVAOA) is the key marker of exposure to high doses of lewisite, whereas chlorovinylarsonous acid (CVAA) is primarily detected in biomedical samples on low-dose exposure
In the present research we explored the possibility of determination of CVAA in the blood plasma, red blood cells and urine of animals after exposure to lewisite followed by antidotal therapy
Summary
Identification and quantification of chemical warfare agents (CWAs) and their metabolic products in biomedical samples is an essential component of the complex measures applied to verification of the implementation of the Chemical Weapons Convention (CWC) [4]. Koryagina et al / High-sensitivity determination of 2-chlorovinylarsonous acid in biomedical samples to 2-chlorovinylarsonic acid (CVAOA) These two acids are lewisite markers, i.e., their detection in biomedical samples provides unequivocal evidence for exposure to lewisite. Vilensky et al [11] suggested that CVAOA is the key marker of exposure to high doses of lewisite, whereas CVAA is primarily detected in biomedical samples on low-dose exposure. These two nonvolatile compounds are impossible to determine separately by GC. In terms of detection of exposure of a human to lewisite, combined determination of CVAOA and CVAA in biomedical samples treated with a reducer is a reasonable approach, since both these compounds are absolute markers of lewisite. Separate determination of CVAOA and CVAA is important for understanding the metabolism of lewisite and for developing schemes of antidotal therapy
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