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氟化物再活化过程在生物样品中沙林和梭曼神经毒剂暴露检测中的应用。

The application of the fluoride reactivation process to the detection of sarin and soman nerve agent exposures in biological samples.

作者信息

Adams T K, Capacio B R, Smith J R, Whalley C E, Korte W D

机构信息

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA.

出版信息

Drug Chem Toxicol. 2004 Feb;27(1):77-91. doi: 10.1081/dct-120027901.

Abstract

The fluoride reactivation process was evaluated for measuring the level of sarin or soman nerve agents reactivated from substrates in plasma and tissue from in vivo exposed guinea pigs (Cava porcellus), in blood from in vivo exposed rhesus monkeys (Macaca mulatta), and in spiked human plasma and purified human albumin. Guinea pig exposures ranged from 0.05 to 44 LD50, and reactivated nerve agent levels ranged from 1.0 ng/mL in plasma obtained from 0.05 LD50 sarin-exposed guinea pigs to an average of 147 ng/g in kidney tissue obtained from two 2.0 LD50 soman-exposed guinea pigs. Positive dose-response relationships were observed in all low-level, 0.05 to 0.4 LD50, exposure studies. An average value of 2.4 ng/mL for reactivated soman was determined in plasma obtained from two rhesus monkeys three days after a 2 LD50 exposure. Of the five types of guinea pig tissue studied, plasma, heart, liver, kidney and lung, the lung and kidney tissue yielded the highest amounts of reactivated agent. In similar tissue and with similar exposure procedures, reactivated soman levels were greater than reactivated sarin levels. Levels of reactivated agents decreased rapidly with time while the guinea pig was alive, but decreased much more slowly after death. This latter chemical stability should facilitate forensic retrospective identification. The high level of reactivated agents in guinea pig samples led to the hypothesis that the principal source of reactivated agent came from the agent-carboxylesterase adduct. However, there could be contributions from adducts of the cholinesterases, albumin and fibrous tissue, as well. Quantitative analysis was performed with a GC-MS system using selected ion monitoring of the 99 and 125 ions for sarin and the 99 and 126 ions for soman. Detection levels were as low as 0.5 ng/mL. The assay was precise and easy to perform, and has potential for exposure analysis from organophosphate nerve agents and pesticides in other animal species.

摘要

对氟化物再活化过程进行了评估,以测量从体内暴露的豚鼠(豚鼠)血浆和组织中的底物、体内暴露的恒河猴(猕猴)血液以及加标的人血浆和纯化的人白蛋白中再活化的沙林或梭曼神经毒剂的水平。豚鼠的暴露剂量范围为0.05至44 LD50,再活化的神经毒剂水平范围从0.05 LD50沙林暴露豚鼠血浆中的1.0 ng/mL到两只2.0 LD50梭曼暴露豚鼠肾脏组织中的平均147 ng/g。在所有低水平(0.05至0.4 LD50)暴露研究中均观察到正剂量反应关系。两只恒河猴在2 LD50暴露三天后,血浆中再活化的梭曼平均值为2.4 ng/mL。在所研究的豚鼠的五种组织类型(血浆、心脏、肝脏、肾脏和肺)中,肺和肾脏组织产生的再活化剂含量最高。在相似的组织和相似的暴露程序下,再活化的梭曼水平高于再活化的沙林水平。在豚鼠存活期间,再活化剂水平随时间迅速下降,但在死亡后下降得慢得多。后一种化学稳定性应有助于法医回顾性鉴定。豚鼠样本中再活化剂的高含量导致了这样的假设,即再活化剂的主要来源来自毒剂 - 羧酸酯酶加合物。然而,胆碱酯酶、白蛋白和纤维组织的加合物也可能有贡献。使用气相色谱 - 质谱系统进行定量分析,对沙林的99和125离子以及梭曼的99和126离子进行选择离子监测。检测水平低至0.5 ng/mL。该测定方法精确且易于操作,具有分析其他动物物种中有机磷酸酯神经毒剂和农药暴露的潜力。

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