Rapid analysis of sulfur mustard oxide in plasma using gas chromatography-chemical ionization-mass spectrometry for diagnosis of sulfur mustard exposure

Sulfur mustard (SM) is the most utilized chemical warfare agent in modern history and has caused more casualties than all other chemical weapons combined. SM still poses a threat to civilians globally because of existing stockpiles and ease of production. Exposure to SM causes irritation to the eyes and blistering of skin and respiratory tract. These clinical signs of exposure to SM can take 6-24 h to appear. Therefore, analyzing biomarkers of SM from biological specimens collected from suspected victims is necessary for diagnosis during this latent period. Here, we report a rapid, simple, and direct quantitative analytical method for an important and early SM biomarker, sulfur mustard oxide (SMO). The method includes addition of a stable isotope labeled internal standard, SMO extraction directly into dichloromethane (DCM), rapid drying and reconstitution of the extract, and direct analysis of SMO using gas chromatography-chemical ionization-mass spectrometry. The limit of detection of the method was 0.1 μM, with a linear range from 0.5 to 100 μM. Method selectivity, matrix effect, recovery, and short-term stability were also evaluated. Furthermore, the applicability of the method was tested by analyzing samples from inhalation exposure studies performed in swine. The method was able to detect SMO from 100% of the exposed swine (N = 9), with no interferences present in the plasma of the same swine prior to exposure. The method presented here is the first of its kind to allow for easy and rapid diagnosis of SM poisoning (sample analysis <15 min), especially important during the asymptomatic latency period.