Improvements of the fluoride reactivation method for the verification of nerve agent exposure
article
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.
Topics
Biological markerCholinesteraseCyclosarinOrganophosphorus compoundPotassium fluorideSarinSomanTabunUnclassified drugCalibrationChemical analysisChemical warfareEnzyme activityGas chromatographyHumanMass spectrometryMethodologyNeurotoxicityPlasmaSolid phase extractionBiological MarkersButyrylcholinesteraseChemical warfare agentsCholinesterase reactivatorsEnvironmental exposureEnvironmental monitoringErythrocytesFluoridesGas Chromatography-Mass SpectrometryHumansReproducibility of resultsSensitivity and specificityCholinesterase, 9001-08-5Cyclosarin, 329-99-7Potassium fluoride, 7789-23-3Sarin, 107-44-8Soman, 96-64-0Tabun, 77-81-6Biological MarkersButyrylcholinesterase, EC 3.1.1.-Chemical Warfare AgentsCholinesterase reactivatorsFluorides
TNO Identifier
237864
ISSN
0146-4760
Source
Journal of Analytical Toxicology, 28(5), pp. 364-371.
Pages
364-371
Files
To receive the publication files, please send an e-mail request to TNO Repository.