Synthesis route attribution of highly toxic ethyl sesquimustard based on non-targeted screening strategy and GC-HRMS

Synthesis route attribution enables accurate source tracing of chemical warfare agents and effective discrimination between distinct synthetic pathways. In the current study, we report for the first time the identification of trace process-related impurities derived from the synthesis of the vesicant ethyl sesquimustard, which is listed in Schedule 1.A.04 of the Chemical Weapons Convention (CWC). Using 1,2-ethanedithiol and 2-mercaptoethanol as precursors, 22 different synthetic routes were designed, and 88 batches of samples were produced through micro-synthesis. Gas chromatography-high resolution mass spectrometry (GC-HRMS) coupled with a non-targeted screening strategy was employed to analyze route-specific compounds. The obtained dataset was further used to train the orthogonal partial least squares discriminant analysis algorithm and generate a classification model consisting of eight sub-models. The verification results showed that the overall classification accuracy of the model was 21/22 (about 95%).