A Single Gas Chromatography/Mass Spectrometry Method for Detection of Individual Enantiomers of a Broad Spectrum of G‐Type Chemical Warfare Nerve Agents

Abstract

The organophosphorus (OP) nerve agents are among the most toxic chemical compounds known. A subset of OP nerve agents known as G‐series compounds (including GA (tabun), GB (sarin), GD (soman) and GF (cyclosarin)) all share a chiral center at the phosphorus atom, resulting in a pair of stereoisomers designated as P(+) and P(−); the in vitro capacity to inhibit acetylcholinesterase as well as the in vivo toxicity of G‐agents is associated predominantly with the P(−) isomer of each compound. We have developed a gas chromatography/mass spectrometry (GC/MS) method to analyze the stereoisomers of all four G‐series nerve agents using a single chiral GC column. This approach allows successful baseline (or near baseline) resolution of each enantiomer of the G‐series agents under the same chromatographic conditions. Based on a variety of approaches, we have assigned each isomer peak as P(+) or P(−). The utility of the method (and variations thereof) was demonstrated by using this approach to determine the stereospecific rates of hydrolysis of GF as catalyzed by the enzyme OPH (from B. diminuta). The method described here will be generally applicable for screening enzymes to identify candidates that promote rapid hydrolysis of G‐agents, and thus may be effective as Bioscavengers of OP nerve agents.Research support: Defense Threat Reduction Agency (DTRA).