A simple derivatization for sensitive LC-ESI-MS detection of unsaturated sulfur mustard degradation products

Sulfur mustard (HD) undergoes elimination reactions in environmental and decontamination scenarios, generating diagnostic unsaturated degradation products including 2-hydroxyethyl-vinyl sulfide (2-HVS) and divinyl sulfide (DVS). The two compounds serve as critical chemical markers for HD verification under the Chemical Weapons Convention (CWC) framework. However, direct analysis of these chemicals by liquid chromatography-electrospray ionization source-mass spectrometry (LC-ESI-MS) faces great challenges because of their intrinsic properties of low polarity, high volatility, and inefficient ionization. A simple derivatization method using bis(pyridine) iodonium tetrafluoroborate (IPy₂BF₄) was developed to address these limitations simultaneously. ESI-MS signal was efficiently improved through introducing a permanent positive charge via quaternary ammonium formation after derivatization. Structural confirmation was achieved through high-resolution mass spectrometry in both full-scan and parallel reaction monitoring (PRM) modes. Derivatization conditions were systematically optimized, and the reaction was completed in 5 min. The quantitative method was developed based on quaternization derivatization and LC-ESI-MS with the perdeuterated IPy₂BF₄ derivative as the internal standard. It exhibited a linear range of 0.100-300 ng/mL (R² ≥ 0.99). The sensitivity of this method in three MS scanning modes was assessed as the lowest limit of detection (LOD) of 0.0100 ng/mL in MRM mode. In combination with a simple extraction protocol, DVS and 2-HVS spiked at 1.00 ng/mL in soil, water, and the simulated 42nd Official OPCW Proficiency Test samples were successfully detected by the developed method. This derivatization strategy was also applied in the LC-ESI-MS detection of the oxidized unsaturated degradation products including divinyl sulfoxide (DVSO) and divinyl sulfone (DVSO₂). This simple quaternization derivatization provides a novel analytical technique for sensitive detection of unsaturated HD degradation products in CWC verification.