Biomedical Sciences Department, Dstl, Porton Down, Salisbury, Wiltshire, SP4 0JQ, U.K.
Toxicol Mech Methods. 2008;18(4):313-21. doi: 10.1080/15376510701884944.
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.
摘要 VX 是一种有效的有机磷化合物，主要通过不可逆地抑制乙酰胆碱酯酶，导致乙酰胆碱积聚，从而产生神经毒剂中毒的特征迹象。VX 是一种低挥发性制剂，因此最有可能通过皮肤吸收进入体内。这项研究首次表明，使用皮肤微透析技术可以跟踪经皮 VX 渗透的时间过程，并且 VX 以浓度依赖的方式被麻醉豚鼠的皮肤吸收。线性微透析探针（5 kDa 截止）被植入豚鼠背部的真皮中，并以 5 μL/min 的速度用生理盐水溶液灌注。将 VX（296 或 592 μg/kg）施用于微透析探针部位（33 μL/kg），并在长达 6 小时内收集透析液样品。通过液相色谱-串联质谱法（LC-MS-MS）测量 VX 透析液浓度。定量范围为 0.1 至 100 ng/mL，校准呈线性。在两种剂量下，VX 均在 15 分钟内被检测到，在施用 VX 后 30 分钟达到峰值。此后，VX 浓度下降。在透析液中，VX 有明显的剂量依赖性恢复，两种剂量之间的总回收量具有统计学意义。这项研究清楚地表明，微透析可以用于跟踪麻醉豚鼠经皮吸收 VX 的时间过程，并将在未来的研究中用于开发改进的医疗对策。英国国防科学技术实验室版权所有（c）2007 年
