Title
Improvements of the fluoride reactivation method for the verification of nerve agent exposure
Author
Degenhardt, C.E.A.M.
Pleijsier, K.
van der Schans, M.J.
Langenberg, J.P.
Preston, K.E.
Solano, M.I.
Maggio, V.L.
Barr, J.R.
Prins Maurits Laboratorium TNO
Publication year
2004
Abstract
One of the most appropriate biomarkers for the verification of organophosphorus nerve agent exposure is the conjugate of the nerve agent to butyrylcholinesterase (BuChE). The phosphyl moiety of the nerve agent can be released from the BuChE enzyme by incubation with fluoride ions, after which the resulting organophosphonofluoridate can be analyzed with gas chromatography-mass spectrometry (GC-MS). This paper describes recent improvements of the fluoride-induced reactivation in human plasma or serum samples by enhancing the sample preparation with new solid-phase extraction cartridges and the MS analysis with large volume injections. Analysis is performed with thermal desorption GC with either mass selective detection with ammonia chemical ionization or high-resolution MS with electron impact ionization. The organophosphorus chemical warfare agents analyzed in this study are O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate, ethyl methylphosphonofluoridate, isopropyl methylphosphonofluoridate (sarin, GB), O-ethyl N,N-dimethylphosphoramidocyanidate, ethyl N,N- dimethylphosphoramidofluoridate, and cyclohexyl methylphosphonfluoridate. Detection limits of approximately 10 pg/mL plasma were achieved for all analytes, which corresponds to 0.09% inhibition with GB on a sample with normal BuChE levels.
Subject
Warfare
Biological marker
Cholinesterase
Cyclosarin
Organophosphorus compound
Potassium fluoride
Sarin
Soman
Tabun
Unclassified drug
Calibration
Chemical analysis
Chemical warfare
Enzyme activity
Gas chromatography
Human
Mass spectrometry
Methodology
Neurotoxicity
Plasma
Solid phase extraction
Biological Markers
Butyrylcholinesterase
Chemical warfare agents
Cholinesterase reactivators
Environmental exposure
Environmental monitoring
Erythrocytes
Fluorides
Gas Chromatography-Mass Spectrometry
Humans
Reproducibility of results
Sensitivity and specificity
Cholinesterase, 9001-08-5
Cyclosarin, 329-99-7
Potassium fluoride, 7789-23-3
Sarin, 107-44-8
Soman, 96-64-0
Tabun, 77-81-6
Biological Markers
Butyrylcholinesterase, EC 3.1.1.-
Chemical Warfare Agents
Cholinesterase reactivators
Fluorides
To reference this document use:
http://resolver.tudelft.nl/uuid:47aae1c4-8386-4555-8e73-96b6e64e5989
TNO identifier
237864
ISSN
0146-4760
Source
Journal of Analytical Toxicology, 28 (5), 364-371
Document type
article