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Evaluation of Respirator Filter Effectiveness by Analysis of Sarin Simulant, Dimethyl Methylphosphonate, From Activated Carbon and Toxicokinetics of Cyanide Exposure in Swine Plasma by Analysis of Cyanide Metaoblite, Alpha-ketoglutarate Cyanohydrin
Chemical warfare agents (CWAs) have the ability to incapacitate and kill. Therefore, the development of analytical assays to detect CWAs is important to verify exposure and to optimize protection technologies. If used properly, protection technologies, including activated carbon (AC) respirator filters, mitigate exposure to CWAs. In order to test their effectiveness, a technique to map the concentration of a toxicant adsorbed inside respirator filters was developed. Specifically, an analytical method to quantify and map dimethyl methylphosphonate (DMMP) concentrations from AC respirator filters was developed and applied to the analysis of several filters. The analysis used a static headspace gas chromatography-mass spectrometry method with a linear range of 2.48-620 g DMMP/kg carbon and a coefficient of variation less than 16%. Several defective filters were tested and the method performed extremely well, correctly identifying the blockage patterns for each filter.
A method to detect the cyanide detoxification product, α-ketogluatrate cyanohydrin (α-KgCN), in swine plasma by ultra-high performance liquid chromatography tandem mass spectrometry was also developed. It was hypothesized that α-KgCN may have significant advantages, as a potential alternative marker for detecting cyanide exposure, over other cyanide exposure markers, such as direct cyanide analysis, thiocyanate, and 2-amino-2-thiazoline-4-carboxylic acid (ATCA). The α-KgCN method produced a limit-of-detection of 200 nM, a linear range of 0.3-50 μM and a relative standard deviation less than 13% in swine plasma. To evaluate α-KgCN as a marker of cyanide exposure, pigs were exposed to KCN (4 mg/mL) intravenously (0.17 mg/kg/min) until apnea was reached and plasma samples were gathered during and after KCN infusion. Plasma α-KgCN concentrations rose steadily during infusion of KCN and then gradually decreased after KCN infusion was stopped. The relative behavior of α-KgCN followed the behavior of cyanide and ATCA in the plasma. Overall, the DMMP method presented here provides a simple, effective and useful technique for evaluating and testing AC performance within a respirator filter for binding DMMP and α-KgCN shows promise as a novel biomarker of cyanide exposure.