Retrospective detection nerve agents

Van der Schans, M.J., Polhuijs, M., Van Dijk, C., Degenhardt, C.E.A.M., Pleijsier, K., Langenberg, J.P., and Benschop, H.P. (2004). Retrospective detection of exposure to nerve agents analysis of phosphofluoridates originating from fluoride-induced reactivation of phosphylated BuChE. Arch. Toxicol., 78, 508-524. 

Figure 11. Fluoride-induced regeneration of sarin from sarin-inhibited BuChE in plasma of a rhesus monkey after IV administration. The rhesus monkey received a final dose of 0.7 p.g/kg (taken from Van der Schans, M J. et al., 2004). Reprinted from Archives of Toxicology, 78 2004, 508-524, Retrospective detection of exposure to nerve agents , by M. J. Van der Schans etal., original copyright notice with kind permission of Springer Science and Business Media...

Retrospective detection of exposure to nerve agents analysis of phosphofluoridates originating from fluoride-induced reactivation of phos-phylated BuChE. Arch Toxicol, 78, 508-524. 

Most methods for determination of these compoimds are based on liquid chromatography or gas chromatography, which require derivatization (Hack and Muir, 2003). Selective MS-MS techniques facilitated by triple quad instruments or ion trap instruments enable the detection of hydrolysis products to the range of pg/mL (Barr et al., 2004 Riches et al., 2005). This concentration is so low that hydrolysis products can be detected in urine up to 1 week after exposure (Riches et al., 2005). Nerve agents bind to proteins such as AChE and butyrylcholinester-ase (BuChE). These proteins are not excreted or metabolized rapidly (typical half-life is 12 days for BuChE) (Hall et al., 1984), which means that adducts to proteins can serve as retrospective biomarkers for exposure to nerve agents (Bidder et al., 2002 van der Schans et al., 2004). The enzymahc measurement of AChE activity, known as the Ellman assay, is the easiest method to determine nerve agent exposure (Ellman et al., 1961 Halbrook et al., 1992). 

Van der Schans et al., 2002). It is based on the rapid isolation of BChE from plasma by affinity chromatography, digestion with pepsin, and followed by liquid chromatography with toe mass spectrometric analysis of phosphylated nonapeptides. The method can be applied for the detection of exposures to various OP pesticides and nerve agents including soman. This approach is very valuable and represents a new field for the improvement of diagnosis with OPs. A comprehensive review of the methods for retrospective detection of exposure to toxic scheduled chemicals has been published by Noort et al. (2001, 2002). 

Animal data indicate that nerve agents rapidly distribute to the brain, lungs, heart, diaphragm, kidneys, liver and plasma. The concentrations in all tissues initially decline rapidly, followed by a second more gradual decline, reflecting metabolism and urinary elimination, respectively. The measurement of the hydrolysis product of sarin [0-isopropyl methylphosphonic acid (IMPA)] in urine may be used for retrospective detection of exposure, although it is... 

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