Distribution and elimination of the stereoisomers of soman and their effect on brain acetylcholine

The four stereoisomers of soman (O-(1,2,2-trimethylpropyl)-methyl-fluorophosphonate) have been analyzed in vivo in mouse blood and tissues after administration of doses corresponding to 0.75 × LD50 of the two diastereoisomeric pairs of soman (S c- and R c-soman). The disappearance of the four isomers has been studied in vitro in the presence of enzymes involved in the toxicity and detoxification of soman, e.g., acetyl- and pseudocholin-esterase, aliesterase, and phosphorylphosphatase. The effect of S c- and R c-soman on brain acetylcholine was studied in the mouse. The analytical methods used are based on gas chromatographymass spectrometry with deuterated internal standards. R cR p- and S cR p-soman, the two isomers that preferentially react with acetylcholinesterase, were found in blood and liver. In liver the concentration of S cR p was higher than that of R cR p and could be followed for 18 hr. In blood only S cR p could be found. Its presence there could be followed during 18 hr. The levels were, however, lower than in liver. The results indicate that the liver might be a depot for soman and that S cR p might be responsible for the delayed intoxication noted after treatment with antidotes. R c-soman was found to have a more pronounced effect on the acetylcholine synthesizing system than has S c-soman, which might explain its higher in vivo toxicity.