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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 32, Number 1, January/February,
pp.125-131
Verification of Exposure to Cholinesterase
Inhibitors: Generic Detection of OPCW Schedule 1 Nerve Agent
Adducts to Human Butyrylcholinesterase
M.J. van der Schans, A. Fidder, D. van
Oeveren, A.G. Hulst, and D. Noort
TNO Defence, Security, and Safety, P.O. Box 45, 2280 AA Rijswijk,
The Netherlands
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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