title: The application of the fluoride reactivation process to the detection of sarin and soman nerve agent exposures in biological samples.
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.
authors.affiliation: US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Adams
authors.forename: B R
authors.initials: BR
authors.lastname: Capacio
authors.forename: J R
authors.initials: JR
authors.lastname: Smith
authors.forename: C E
authors.initials: CE
authors.lastname: Whalley
authors.forename: W D
authors.initials: WD
authors.lastname: Korte
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007928:Lethal Dose 50; D008253:Macaca mulatta; D012524:Sarin / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D012999:Soman / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D012999:Soman; D012524:Sarin; D005459:Fluorides