Nerve agents alkyl methylphosphonic acids

M. Katagi, M. Tatsuno, M. Nishikawa and H. Tsuchihashi, On-line solid-phase extraction liquid chromatography-continuous flow frit fast atom bombardment mass spectrometric and tandem mass spectrometric determination of hydrolysis products of nerve agents alkyl methylphosphonic acids by p-bromophenacyl derivatization, J. Chromatogr., A, 833, 169-179 (1999). 

The metabolism of nerve agents is much simpler than that of sulfur mustard. The major pathway for elimination is via enzyme-mediated hydrolysis by esterases, plus some chemical hydrolysis, as shown in Figure 10. In the case of the methylphosphonofluoridates and V agents, the major product is an alkyl methylphosphonic acid (alkyl MPA) (16). A small fraction of the nerve agent binds... 

Rodin, I.A., Shpak, A.V., Shpigim, O.A., Rybalchenko, I.V., Savelieva, E.I. (2007). Highly sensitive determination of alkyl methylphosphonic acids - degradation products of chemical warfare nerve agents by HPLC-MS in rats plasma. European Conference on Analytical Chemistry Euroanalysis XIV , Antwerpen, Belgium, September 9-14, 684 pp. 

FIGURE 19.2 Hydrolysis pathway of sarin (GB), soman (GD), and cyclosarin (GIO hydrolysis pathway of nerve agents proceeds through the alkyl methylphosphonic acids, isopropyl methylphosphonic acid (IMPA), pinacolyl methylphosphonic acid (PMPA), and cyclohexyl methylphosphonic acid (CMPA) to methylphos-ponic acid (MPA). Analysis of the alkyl methylphosphonic acids allows identification of the parent agent, while assay of MPA is nonspecific. 

The alkyl methylphosphonic acids provide a convenient marker for determining exposure to nerve agents. Numerous modifications for the assay of these compounds have been developed for blood or urine, and several have been applied to actual human exposure cases. Important factors in considering this test are extent of exposure and time following the event. One of the most severely poisoned victims of the Matsumoto sarin attack demonstrated measurable IMPA in the urine on the seventh day. To put the severity of this case in perspective, AChE values were in the range of 5%-8% of normal (Nakajima et al., 1998). However, in most cases, hydrolysis products should not be considered to be present for more than 24-48 h following exposure. The methods used to verify human exposure to nerve agents based on assay of hydrolysis products are presented in Table 19.2. 

Miki A, Katagi M, Tsuchihashi H et al. (1999). Determination of alkyl methylphosphonic acids, the main metabohtes of organophosphorus nerve agents, in biofluids by gas chromatography-mass spectrometry by liquid-liquid-solid-phase-transfer-catalyzed pentafluorobenzylation. J Anal Toxicol, 23, 86-93. 

New GC and GC-MS methods reported during 2011 include a GC-MS patent for detecting the content of a special flame retardant, trw(aziridinyl) phosphine oxide (TEPA) in textiles, a determination of organophosphate pesticides in water and soil using ultrasormd-assisted emulsification microextraction (USAEME) followed by GC analysis, and a direct GC-FID method for free alkyl methylphosphonic acids from hydrolysis of chemical nerve agents. ... 

Environmental Fate. The primary degradation mechanism for nerve agents in the environment is hydrolysis to the corresponding alkyl methylphosphonate, followed, for most of the agents, by slow hydrolysis to methyl phosphonic acid. The alkyl methylphosphonates may persist for years in the environment. Degradation or decomposition in soil may be faster than in water as a result of the variety of available processes and catalysts. 

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