The Application of a Single-Column GC-MS-MS Method for the Rapid Analysis of Chemical Warfare Agents and Breakdown Products.

The development of one comprehensive gas chromatographic-triple quadrupole mass spectrometric (GC-MS-MS) method for the analysis of nerve agents and their breakdown products can pose a challenge due to significant differences in analyte volatility. Nerve agent breakdown products typically have a low volatility, requiring a derivatization step prior to analysis by gas chromatography (GC). However, nerve agent parent compounds are generally more volatile, which eliminates the need for derivatization and allows for direct analysis. Therefore, the analysis of these analytes is typically performed using separate analytical methods. This may require the use of multiple columns composed of different stationary phases to ensure the most efficient separation. With the wide selection of GC columns and derivatizing agents, it is potentially possible to develop a single-column/analytical method that is suitable for the detection of nerve agents and their breakdown products. We evaluated six nerve agents (tabun, sarin, soman, cyclosarin, VX and Russian VX) and the six corresponding breakdown products (EDPA, IMPA, PMPA, CMPA EMPA and MMPA). Chromatographic separation and multiple-reaction mode electron ionization detection of the nerve agents and silylated breakdown product derivatives were performed using an Agilent 7890 A gas chromatography (GC) equipped with a mid-polarity column, coupled to a 7000 triple quadrupole mass spectrometry system. A fast (12.5 min), highly sensitive (picogram) and selective method was achieved. The feasibility of this method for nerve agent and breakdown product detection in real samples was demonstrated using nerve agent-spiked human plasma at various exposure times (3 min, 1 h and 24 h). Five of the six nerve agents and all six breakdown products were successfully detected. This robust method has utility as a rapid screening tool to identify a specific nerve agent in a potential exposure event by simultaneous detection of the parent and or its corresponding breakdown product in plasma.