title: Quantification of nerve agent VX-butyrylcholinesterase adduct biomarker from an accidental exposure.
abstract: The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80 nM, it can be calculated that inhibition levels of >or= 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.
authors.affiliation: Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, Georgia 30341, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Solano
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Thomas
authors.forename: James T
authors.initials: JT
authors.lastname: Taylor
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: McGuire
authors.forename: Edward M
authors.initials: EM
authors.lastname: Jakubowski
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Thomson
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Maggio
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Holland
authors.forename: J Richard
authors.initials: JR
authors.lastname: Smith
authors.forename: Benedict
authors.initials: B
authors.lastname: Capacio
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Woolfitt
authors.forename: David L
authors.initials: DL
authors.lastname: Ashley
authors.forename: John R
authors.initials: JR
authors.lastname: Barr
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002138:Calibration; D002619:Chemical Warfare Agents / Q000032:analysis / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000097:blood / Q000378:metabolism; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring / Q000379:methods*; D005459:Fluorides / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D009946:Organothiophosphorus Compounds / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D017680:Potassium Compounds / Q000737:chemistry
chemical_list: D015415:Biomarkers; D002091:Butyrylcholinesterase; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D005459:Fluorides; D009946:Organothiophosphorus Compounds; D017680:Potassium Compounds; C033320:potassium fluoride; C009680:VX-agent