Determination of tissue distribution of VX and its metabolites EMPA and EA-2192 in various rat tissues by LC-ESI-MS/MS after phosphotriesterase treatment.

Phosphotriesterases (PTE) are a new and promising approach for the treatment of organophosphate poisoning, since the current therapy of such intoxications shows some limitations. A previous rat in vivo study confirmed the therapeutic effect of PTE, which were specifically designed for VX breakdown, and demonstrated rapid degradation of VX in whole blood samples. The present study now focuses on the degradation of VX and its distribution in organ tissues of the animals used in the aforementioned study. In order to gain a broader overview, we have extended the investigations to the VX metabolites EA-2192 and EMPA by using methods developed for an LC-ESI-MS/MS system. Applying these methods, we were able to verify the effectiveness of the PTE treatment and gained an overview of VX tissue distribution in poisoned but untreated rats. • Rat tissue samples after VX and phosphotriesterase administration were studied. • The distribution of VX, EMPA, EA-2192 in various rat tissues was studied. • Modified LC-ESI-MS/MS methods were applied. • PTE administration results in markedly lower or even absent VX tissue levels. • An overview of tissue distribution of EMPA and EA-2192 was gained. [ABSTRACT FROM AUTHOR]