The major metabolites and breakdown products of some toxic organophosphonates are their respective alkymethylphosphonic acids. These acids ionize at physiological pH and are not amenable to gas chromatographic analysis in their underivatized forms. Their detection in biological samples has been difficult because of their presence at only trace levels. Existing analytical methods were developed mainly for measuring these phosphonic acids in environmental samples and at higher concentrations. In this study, we devised a gas chromatographic/mass spectrometric method to provide confirmation and quantification of the organophosphonic acids of soman (GD), sarin (GB) and GF in blood and urine. This report describes the various derivatization conditions that we have studied and demonstrates the characteristic mass spectra by different ionization techniques.

This study reports on the pharmacokinetics of the elimination of the metabolites of three toxic organophosphorus compounds (soman, sarin and GF). Urine, blood and lung tissue were collected from rats dosed subcutaneously at 75 micrograms kg-1. Urinary excretion of the metabolite was the major elimination route for these three compounds. The major differences among them were primarily the extent and rate of excretion. The hydrolyzed form, alkylmethylphosphonic acid, was the single major metabolite formed and excreted in urine by a non-saturable mechanism. Nearly total recoveries of the given doses for sarin and GF in metabolite form were obtained from the urine. The terminal elimination half-lives in urine were 3.7 +/- 0.1 and 9.9 +/- 0.8 h for sarin and GF, respectively. Soman metabolite showed a biphasic elimination curve with terminal half-lives of 18.5 +/- 2.7 and 3.6 +/- 2.2 h. Soman was excreted at a slower rate with a recovery of only 62%. Lung was the major organ of accumulation for soman. In blood the toxic agents were concentrated more in red blood cells than in plasma. The acid metabolites can serve as a better chemical marker for monitoring organophosphorus exposure in humans via their higher concentration and longer half-life in urine than the parent compounds.

Reduction of (OC)gCo3CCO+PF6~with Triethylsilane. (a) In the Absence of Aluminum Chloride. The acylium hexafiuorophosphate prepared from 2.0 mmol of (OC)9Co3CC02Et was slurried in 20 ml of dichloromethane under nitrogen, and 0.80 g (6.6 mmol) of triethylsilane (PCR Inc.) was added. The mixture was stirred at room temperature for 1 hr; a homogeneous solution resulted.The reaction mixture was evaporated under reduced pressure and the residue was extracted with hexane. The red extracts were filtered through a layer of silicic acid and evaporated. The red solid residue was sublimed in vacuo at 50°to give 0.65 g of red solid, melting in the range 95-115°with decomposition. Its ir spectrum suggested that a mixture of CH3CCo3(CO)9 and HCCo3(CO)9 was present (bands at 2960 w, 2920 m, 2880 m, 2820 m, 1160 m, 1000 s, and 855 m cm-1). The entire sample was dissolved in deuteriochloroform and the nmr spectrum which was taken showed that these two products were present in 1 to 1.44 ratio (30 and 43% yields, based on the 0.65 g isolated), respectively, by integration of the resonances at 6 3.76 and 12.10 ppm.(b) In the Presence of Aluminum Chloride. The acylium hexafluorophosphate was prepared from 2.0 mmol of (OC)9Co3CC02-Et and slurried in 15 ml of dichloromethane under nitrogen. To this mixture was added 0.75 g (6.0 mmol) of aluminum chloride. A brief evolution of gas commenced but subsided quickly. Addition of 0.70 g (6.0 mmol) of triethylsilane followed. A brief evolution of gas again was observed and the solution turned from brown to red-brown. Tic (benzene) showed the presence of a single brown material in the solution. After it had been stirred for 10 min at room temperature, the mixture was treated with 150 ml of 15% aqueous HC1 and extracted with 100 ml of dichloromethane.The organic layer was dried and evaporated. The brown solid which remained was taken up in benzene. This solution was passed through a layer of silicic acid and evaporated. The residue was recrystallized from hexane to give 0.68 g (74%) of black needles which decomposed without melting around 115°and whose ir spectrum was identical with that of an authentic sample11 of the aldehyde, (OC)9Co3CCHO.An experiment in which only 2 mmol of aluminum chloride was added to the acylium hexafiuorophosphate prepared from 2 mmol of the cluster-ester and in which this mixture was treated with 6 mmol of triethylsilane gave only CH3CCo3(CO)9 (25%) and HCCo3(CO)9 (45 %) and none of the aldehyde.Reaction of (OC)gCo3CC02CH2C==CCH202CCCo3(CO)g with Dicobalt Octacarbonyl. A 100-ml three-necked flask equipped with a magnetic stirring unit, a nitrogen inlet tube, and a no-air stopper was charged with a solution of the cluster-substituted acetylene (0.42 g, 0.47 mmol) in 20 ml of anhydrous diethyl ether. Subsequently, a solution of 2.3 g (6.7 mmol) of dicobalt octacarbonyl in 50 ml of diethyl ether was added. The mixture was stirred under nitrogen at room temperature for 90 min, during which time a very slow gas evolution and the separation of a solid were observed. The so...

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