Methylphosphonic acids agents

The Newport, Indiana, stockpile contains 1,269 tons of VX nerve agent, a relatively nonvolatile, persistent toxin that disrupts signal transmission in the central nervous system. VX can be hydrolyzed in hot aqueous sodium hydroxide solution. This process produces a strongly alkaline solution containing salts of methylphosphonic acid, its monoethyl ester, and a foul-smelling thiol amine compound. In 1996, the NRC recommended further evaluation of the Army s... 

Methylphosphonic acid (MPA), a degradation product of gas chemical warfare agents, such as sarin (isopropyl methylphosphonofluoridate), soman or VX (0-ethy I -.S -2-di isopropyl am i noethvl methyl phosphonoth ioate), has been recognized selectively by an MIP chemosensor using potentiometric transduction (Table 6) [181]. The MIP preparation involved co-adsorption, in ethanol, of the methylphosphonic acid (MPA) template and octadecyltrichlorosilane, followed by silanization on the indium-tin oxide (ITO) electrode surface in the chloroform-carbon tetrachloride solution at 0 °C. Subsequently, the electrode was rinsed with chloroform to remove the template. A potential shift due to the presence of MPA was significant as compared to that due to interferants like methyl parathion, dimethoate, phosdrin, malathion, etc. The linear concentration range varied from 50 pM to 0.62 M MPA at LOD as low as 50 pM and an appreciably short response time of 50 s. 

Katagi, M., Nishikawa, M., Tatsuno, M and Tsu-chihashi, H. Determination of the main hydrolysis products of organophosphorous nerve agents, methylphosphonic Acids, in human serum by indirect photometric detection ion chromatography, J. Chromatogr., B, 698, 81 (1997). 

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... 

Agent GD may hydrolyze to relatively nontoxic hydroflouric and pinacolyl methylphosphonic acids (MacNaughton and Brewer, 1994 Rosenblatt et al., 1995). The hydrolysis rate is a function of temperature and pH the rate is minimum between pH 4 and 6. The C/2 for GD is approximately 100 hours with 20 x ti/2 being required to attain a 1 x 10 reduction in GD concentration. 

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. 

In addition, due to the reversibility of the binding reaction of sarin and soman to CarbE, it appears that CarbEs are involved in metabolic detoxification of these agents to their corresponding nontoxic metabolites isopropyl methylphosphonic acid (IMPA) and pinacolyl methylphosphonic acid (PMPA) (Jokanovic et al, 1996). 

FIGURE 52.1. Metabolic detoxification of warfare nerve agents tabun, sarin, soman, and VX in mammals in vivo. Chemical names of metabolites are EDMPA - ethyl dimethylaminophosphoric acid, IMPA - isopropyl methylphosphonic acid, PMPA - pinacolyl methyl-phosphonic acid, EMPA - ethyl methylphosphonic acid, and MPA - methylphosphonic acid. 

The elimination of VX deviates from that of soman. As observed in the toxicokinetic smdies, the elimination of VX proceeds much slower than that for the G-agents. In addition to the major detoxification route of VX, which leads to the formation of 0-ethyI methylphosphonic acid, it cannot be excluded that toxic metabolites will be formed. Possible toxic metabolites are the deal-kylated form of VX or desethyl-VX and the N-oxide of VX. Neither metabolite has been found in blood samples taken for toxicokinetic experiments. In vitro experiments, in which high concentrations of VX (10 p,g/mL) were incubated in plasma or fiver homogenate, did not yield any of these toxic metabolites either. However, desethyl-VX could be detected in reasonable amounts when plasma was derived from blood that was drawn in mbes with EDTA as anticoagulant. EDTA binds metal ions that are essential for the enzymatic hydrolysis of VX, which leads to the formation of EMPA. When that route is inhibited, the formation of desethyl-VX may increase. ... 

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. 

Agent GB isopropyl methylphosphonic acid methylphosphonic acid... 

---