title: 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.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany. georgreiter@bundeswehr.org
authors.forename: Georg
authors.initials: G
authors.lastname: Reiter
authors.forename: John
authors.initials: J
authors.lastname: Mikler
authors.forename: Ira
authors.initials: I
authors.lastname: Hill
authors.forename: Kendal
authors.initials: K
authors.lastname: Weatherby
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006801:Humans; D016014:Linear Models; D008297:Male; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine; D053719:Tandem Mass Spectrometry; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D002800:Cholinesterase Inhibitors; D009946:Organothiophosphorus Compounds; C009680:VX-agent