Verification of exposure to cholinesterase inhibitors: Generic detection of OPCW schedule 1 nerve agent adducts to human butyrylcholinesterase

article




Schans, M.J. van der

Fidder, A.

Oeveren, D. van

Hulst, A.G.

Noort, D.
Phosphylated butyrylcholinesterase is one of the most important biomarkers to verify an exposure to nerve agents, and it can be analyzed with liquid chromatography-tandem mass spectrometry (LC-MS-MS) by detection of a phosphylated nonapeptide that results after digestion of butyrylcholinesterase (BuChE) with pepsin. For a sensitive analysis (low degree of BuChE inhibition), the identity of the cholinesterase inhibitor has to be known in order to use the LC-MS-MS instrument in the most sensitive selected reaction monitoring mode. In practice, the identity of the cholinesterase inhibitor will not be known beforehand, and the number of possible organophosphates is greater than 1000. However, the number of possible molecular masses of organophosphates is approximately 170. A method for which only 34 transitions in the multiple reaction monitoring mode have to be acquired in order to screen for an exposure to all Organization for the Prohibition of Chemical Weapons Schedule 1 nerve agents was developed.
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CholinesteraseCholinesterase inhibitorNerve gasNonapeptideOrganophosphatePepsin AArticleChemical warfareControlled studyHumanLiquid chromatographyTandem mass spectrometryBiological MarkersButyrylcholinesteraseChemical Warfare AgentsCholinesterase InhibitorsChromatography, LiquidEnvironmental ExposureEnvironmental MonitoringHumansOrganophosphorus CompoundsOrganothiophosphorus CompoundsPepsin APeptidesPhosphoric Acid EstersReproducibility of ResultsSarinTandem Mass SpectrometryCholinesterase, 9001-08-5Pepsin A, 9001-75-6Biological MarkersButyrylcholinesterase, EC 3.1.1.-Chemical Warfare AgentsCholinesterase InhibitorsCyclohexyl methylphosphonofluoridate, 329-99-7Organophosphorus CompoundsOrganothiophosphorus CompoundsPepsin A, EC 3.4.23.1PeptidesPhosphoric Acid EstersSarin, 107-44-8Tabun, 77-81-6VX, 50782-69-9
TNO Identifier
183467
Repository link
https://resolver.tno.nl/uuid:cf04a32d-24ae-4dd0-9022-15861aa95f37
ISSN
0146-4760
Source
Journal of Analytical Toxicology, 32(1 (January/February)), pp. 125-130.
Pages
125-130
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