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Simultaneous quantification of VX and its toxic metabolite in blood and plasma samples and its application for in vivo and in vitro toxicological studies.

Abstract
The present study was initiated to develop a sensitive and highly selective method for the simultaneous quantification of the nerve agent VX (O-ethyl S-[2(diisopropylamino)ethyl] methylphosphonothioate) and its toxic metabolite (EA-2192) in blood and plasma samples in vivo and in vitro. For the quantitative detection of VX and EA-2192 the resolution was realized on a HYPERCARB HPLC phase. A specific procedure was developed to isolate both toxic analytes from blood and plasma samples. The limit of detection was 0.1 pg/ml and the absolute recovery of the overall sample preparation procedure was 74% for VX and 69% for EA-2192. After intravenous and percutaneous administration of a supralethal doses of VX in anaesthetised swine both VX and EA-2192 could be quantified over 540 min following exposure. This study is the first to verify the in vivo formation of the toxic metabolite EA-2192 after poisoning with the nerve agent VX. Further toxicokinetic and therapeutic studies are required in order to determine the impact of EA-2192 on the treatment of acute VX poisoning.
AuthorsGeorg Reiter, John Mikler, Ira Hill, Kendal Weatherby, Horst Thiermann, Franz Worek
JournalJournal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 879 Issue 26 Pg. 2704-13 (Sep 15 2011) ISSN: 1873-376X [Electronic] Netherlands
PMID21862421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Cholinesterase Inhibitors
  • Organothiophosphorus Compounds
  • VX
Topics
  • Animals
  • Cholinesterase Inhibitors (administration & dosage, blood, metabolism, toxicity)
  • Chromatography, High Pressure Liquid
  • Guinea Pigs
  • Humans
  • Linear Models
  • Male
  • Mice
  • Organothiophosphorus Compounds (administration & dosage, blood, metabolism, toxicity)
  • Rabbits
  • Rats
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Swine
  • Tandem Mass Spectrometry
  • Toxicity Tests, Acute (methods)

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