Retrospective Detection of Exposure to Organophosphates: Analyses in Blood of Human Beings and Rhesus Monkeys

Polhuijs, Martine; Langenberg, J.P.; Noort, Daan; Hulst, A.G.; Benschop, H. P.; Jong, L.P.A. de

doi:10.1007/978-94-011-4641-8_40

Cited by 5 publications

(2 citation statements)

References 5 publications

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“…Those methods include monitoring decreases in blood cholinesterase levels,[ 21 residual nerve agent in blood, 1 31 hydrolysis products of the nerve agent, 1 4-6 1 fluoride reactivated species, [7][8][9] and agent adducts of proteins. [' 01 Because the fluoride reactivation process has been shown to be specific, quantitative, retrospective and relatively simple for the analysis of satin exposures, t7 , 8 1 we have evaluated the application of that process to the analysis of soman and satin exposures with guinea pigs (Cava porcellus) and rhesus monkeys (Macaca mulatta) (hereafter referred to as non-human primates, NHP).…”

Section: Introductionmentioning

confidence: 99%

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

Adams¹,

Capacio²,

Smith³

et al. 2004

Drug and Chemical Toxicology

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information 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 LD5 0 , and reactivated nerve agent levels ranged from 1.0 ng/mL in plasma obtained from 0.05 LD 50 sarinexposed guinea pigs to an average of 147 ng/g in kidney tissue obtained from two 2.0 LD 50 soman-exposed guinea pigs. Positive dose-response relationships were observed in all low-level, 0.05 to 0.4 LD 50 , 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 LD 50 exposure. Of the five types of guinea pig

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Section: Introductionmentioning

confidence: 99%

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

Adams¹,

Capacio²,

Smith³

et al. 2004

Drug and Chemical Toxicology

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show abstract

“…Several approaches have been explored to verify nerve agent exposure, including measuring the decrease in acetylcholine esterase (AChE) activity in blood [2][3][4], analysis of hydrolysis products of the parent agents [5][6][7][8][9], fluoride reactivation of bound agent [10][11][12][13], and analysis of nerve agent adducts [14][15][16][17][18][19][20][21]. A decrease in AChE activity occurs when the nerve agent binds with the active site of the enzyme ( Figure 1, Reaction A; AChE denoted by R'-OH).…”

Section: Introductionmentioning

confidence: 99%

Analysis of nerve agent metabolites from nail clippings by liquid chromatography tandem mass spectrometry

Appel

Logue

2016

Journal of Chromatography B

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While several methods for the bioanalysis of nerve agents or their metabolites have been developed for the verification of nerve agent exposure, these methods are generally limited in the amount of time after an exposure that markers of exposure can be detected (due to rapid metabolism from biological matrices). In this study, a method for the analysis of nerve agent hydrolysis products from nail clippings was developed to allow evaluation of nails as a long-term repository of these markers. Pinacolyl methylphosphonic acid (PMPA) and isopropyl methylphosphonic acid (IMPA) were extracted from nail samples with N,N-dimethylformamide and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Limits of detection for PMPA and IMPA were 0.3μg/kg and 7.5μg/kg and linear ranges were 0.75-300μg/kg and 30-1500μg/kg, respectively. Precision was within 10% and 8% for PMPA and IMPA, respectively, and accuracy was 100±12% for both analytes. The approach presented here is complementary to current methods for nerve agent exposure verification, and should allow for long-term determination of nerve agent poisoning.

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Mass Spectrometry Applications for the Identification and Quantitation of Biomarkers Resulting from Human Exposure to Chemical Warfare Agents

Smith

Capacio²

2010

NATO Science for Peace and Security Series A: Chemistry and Biology

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Retrospective Detection of Exposure to Organophosphates: Analyses in Blood of Human Beings and Rhesus Monkeys

Cited by 5 publications

References 5 publications

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

The Application of the Fluoride Reactivation Process to the Detection of Sarin and Soman Nerve Agent Exposures in Biological Samples

Analysis of nerve agent metabolites from nail clippings by liquid chromatography tandem mass spectrometry

Mass Spectrometry Applications for the Identification and Quantitation of Biomarkers Resulting from Human Exposure to Chemical Warfare Agents

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