VX Penetration Following Percutaneous Poisoning: A Dermal Microdialysis Study in the Guinea Pig

ABSTRACTVX, a potent organophosphorus compound, acts primarily by irreversibly inhibiting acetylcholinesterase resulting in an accumulation of acetylcholine, which produces the characteristic signs of nerve agent poisoning. VX is a low-volatility agent, and therefore the most likely route of absorption into the body is via the skin. This study demonstrates for the first time that it is possible to follow the time course of percutaneous VX penetration using the technique of dermal microdialysis and that VX is absorbed through the skin of the anesthetized guinea pig in a concentration-dependent manner. A linear microdialysis probe (5-kDa cut-off) was implanted in the dermis of the back of the guinea pig and perfused (5 μL/min) with physiological Ringer's solution. VX (296 or 592 μg/kg) was applied (33 μL/kg) over the site of the microdialysis probe and dialysate samples collected for up to 6 h. The VX dialysate concentration was measured by liquid chromatography–tandem mass spectrometry (LC-MS-MS). Quantita...