Mass spectrometric methods for analyses of blister and choking agent markers

Identification of the alleged use of toxic chemicals in chemical weapons is demanding. The lack of verification methods for analysing nitrogen mustards and chlorine in biomedical and environmental samples prompted the development of methods for the preparedness of the Organisation for the Prohibition of Chemical Weapons (OPCW) designated laboratories in their investigation of the alleged use of these toxic chemicals. The methods developed will assist the OPCW in verification of chemical weapons used for the attack. The aims of this research are to develop methods for identifying markers of nitrogen mustards and chlorine exposure using mass spectrometry. The research included development of sample preparation methods, optimisation of instrumental methods, and data analysis strategies, unique to the analysis of nitrogen mustards and chlorine. In addition, efforts have been made to investigate and identify potential new metabolites and markers associated with exposure to nitrogen mustards and chlorine. Methods for ethanolamines, hydrolysis products of nitrogen mustards from urine samples, were developed using targeted analysis. The conjugation of nitrogen mustards with glutathione were also investigated in in vitro. The confirmation of the nitrogen mustards-glutathione conjugates such as monoglutathionyl, diglutathionyl, and phosphorylated conjugates for each nitrogen mustards was verified by the liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) in the product ion scan mode. Markers for chlorinated concrete samples from various origins and ages were investigated to identify reaction products of chlorine after treatment with different chlorination agents like bleach and chlorine gas at different concentrations, using MS/MS and HRMS instruments in multiple reaction monitoring and full scan modes, respectively. Tetrachlorophenol and trichloromethylbenzene, two chemicals specific to neat chlorine gas, were identified in these chlorinated concrete extracts. In this study, data was further analysed using multivariate analysis, and chemical pattern recognition resulted in distinct and distinguishable chemical groups. Chlorinated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholines (POPC) were studied using LC-HRMS/MS and provided unequivocal lipid biomarkers after chlorine gas exposure. This research will offer insight into the methodologies for analysing nitrogen mustards and chlorine markers, providing a comprehensive overview of the current state of research for these chemicals. The research contributed significant scientific knowledge to the identification of markers of nitrogen mustards and chlorine in biomedical and environmental samples.

Grantor dc:publisher

Helsingin yliopisto

Year dc:date.issued

2024

Author dc:creator

• Hamzah, Nurhazlina

• mass Spectrometry

Statement dc:rights

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Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10138/570399

OAI record oai:identifier

https://helda.helsinki.fi/server/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ahelda.helsinki.fi%3A10138%2F570399