Title
Verification of exposure to organophosphates: Generic mass spectrometric method for detection of human butyrylcholinesterase adducts
Author
Noort, D.
Fidder, A.
van der Schans, M.J.
Hulst, A.G.
TNO Defensie en Veiligheid
Publication year
2006
Abstract
We present a generic mass spectrometric method to verify exposure to organophosphates, based on the chemical conversion of the phosphylated peptides obtained after pepsin digestion of human butyrylcholinesterase (HuBuChE) to a common precursor peptide. After exposure of plasma to various organophosphates (nerve agents, pesticides), HuBuChE was isolated from plasma by procainamide affinity-based solid-phase extraction. Upon subsequent pepsin digestion, the respective phosphylated nonapeptides could be identified in the digests. After treatment of the pepsin digests with Ba(OH)a in the presence of a nucleophilic tag (a thiol or amine), the phosphylated nonapeptides were transformed into a common tagged nonapeptide that could be analyzed sensitively by means of LC tandem MS. So far, best results were obtained with 2-(3-aminopropylamino)ethanol as nucleophilic tag. By applying the presented method, HuBuChE inhibition can now be monitored accurately by mass spectrometry, without advance knowledge of the structure of the inhibitor. © 2006 American Chemical Society.
Subject
Enzyme inhibition
Ethanol
Mass spectrometry
Phosphates
Plasmas
Proteins
Generic mass spectrometric
Human butyrylcholinesterase adducts
Organophosphates
Phosphylated peptides
Biochemistry
Cholinesterase
Cholinesterase inhibitor
Dichlorvos
Methylphosphonothioic acid s (2 diisopropylaminoethyl) o ethyl ester
Nerve gas
Nonapeptide
Organophosphate pesticide
Organophosphorus compound
Pepsin A
Phosphoserine
Procainamide
Proton
Sarin
Soman
Analytic method
Article
Biological monitoring
Chemical warfare
Cholinesterase inhibition
Human
Liquid chromatography
Plasma
Solid phase extraction
Spectrometer
Tandem mass spectrometry
Terrorism
Time of flight mass spectrometry
Butyrylcholinesterase
Chromatography, Liquid
Humans
Phosphoric Acid Esters
Solid Phase Extraction
Tandem Mass Spectrometry
To reference this document use:
http://resolver.tudelft.nl/uuid:3810e201-9178-4ca3-88a0-555e1b656f76
DOI
https://doi.org/10.1021/ac060954t
TNO identifier
239480
ISSN
0003-2700
Source
Analytical Chemistry, 78 (18), 6640-6644
Document type
article