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Analytical approaches for monitoring exposure to organophosphorus and carbamate agents through analysis of protein adducts
Author(s) -
Schopfer Lawrence M.,
Lockridge Oksana
Publication year - 2012
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.1325
Subject(s) - butyrylcholinesterase , chemistry , adduct , nerve agent , chromatography , carbamate , cholinesterase , paraoxon , mass spectrometry , organophosphate , acetylcholinesterase , soman , organic chemistry , enzyme , pharmacology , pesticide , medicine , aché , agronomy , biology
Appropriate treatment of a poisoned patient requires knowing the identity of the poison. This review summarizes the methods for identifying poisoning by organophosphorus and carbamate poisons. Mass spectrometry methods identify the poison from the adducts they form with proteins in blood. The most sensitive method uses potassium fluoride to release the organophosphorus agent from its covalent binding to serine 198 of human butyrylcholinesterase. The released poison is identified by gas chromatography–mass spectrometry. The drawback of this method is that it does not detect exposure to agents such as soman, because butyrylcholinesterase adducts with these agents age to a non‐reactivatable form. A method that detects both aged and non‐aged organophosphylated adducts as well as carbamate adducts is one that digests butyrylcholinesterase with a protease and analyzes the modified peptide by mass spectrometry. This method does not distinguish between poisons that have the same mass after reaction with butyrylcholinesterase – for example, between exposure to chlorpyrifos oxon and paraoxon. Albumin forms a stable, covalent bond with organophosphates on tyrosine 411. The rate of reaction with albumin is much slower than with butyrylcholinesterase, but albumin adducts persist for a longer time in the circulation; they do not age; and they do not release the organophosphate when a patient is treated with an oxime. Copyright © 2012 John Wiley & Sons, Ltd.