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

ABSTRACT VX, 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 muL/min) with physiological Ringer's solution. VX (296 or 592 mug/kg) was applied (33 muL/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). Quantitation was performed over the range 0.1 to 100 ng/mL and the calibration was linear. VX was detected within 15 min, reaching a peak at 30 min following both VX doses. After this time the VX concentration decreased. There was a clear dose-dependent recovery of VX in the dialysate and the total amount recovered was statistically significant between the two doses. This study has clearly shown that microdialysis can be used to follow the time course of the percutaneous absorption of VX in the anesthetized guinea pig and will be used in future studies to develop improved medical countermeasures. Crown Copyright (c) 2007 Dstl.