Reproducibility nerve agents

Reproducibility of the relative intensities in El mass spectra is a concern, despite the fact that spectra are recorded under standardized conditions. Different mass spectrometers produce spectra with, sometimes, large spreads in the relative intensities. An impression of the possible variation is given in Table 2. In this table, the relative intensities of major fragments in the El mass spectra of three nerve agents, taken from three different sources, are presented. It is clear that there exist no reference mass spectra of these Schedule 1 chemicals, which can be considered as true physical constants. A compilation of more than one spectrum of the same compound in the OPCW Analytical Database gives an indication of the possible spread. 

Determination of Nerve Agents In contrast to those rather unusual methods, GC coupled to diverse detection systems, e.g. flame ionization detector (FID), nitrogen-phosphorus detector (NPD), flame photometric detector or mass spectrometer, as well as liquid chromatographic (LC) methods, represent the most common techniques for OP determination especially for biological samples. These methods offer high resolution, sufficient limits of detection, good reproducibility, and robust hardware devices. For more detailed information readers are referred to recent review articles (Hooijschuur et al, 2002 John et al, 2008). 

Table 1. Possible targets for nerve agents in warfare." Adapted and reproduced from Chapter 34, Qrganophosphorus compounds as chemical warfare agents , by Maynard RL and Beswick F, in Clinical and Experimental Toxicology of Organophosphates and Carbamates (B Ballantyne and TC Marrs, eds), 1992, with the kind permission of the publishers, Elsevier, and the authors...

OPs and CMs are used as pesticides, and some OPs are also potential warfare nerve agents. Pesticides are used worldwide, and warfare agcni.s may also be used extensively. To detect absorption of anticholinesterases, a standardized protocol for measuring AChE and BuChE activities in human blood is needed that is simple in technical terms but reliable and well reproducible. This would enable a better comparison of data from different laboratories and an exchange of samples for analysis and confirmation of results. It seems that a protocol based on the Ellman method would meet the outlined requirements, but further studies including interlaboratory quality control are required, particularly when field methods are developed. 

Although the MINICAM system can detect VX, we were unable to develqi a quantitative penetration cell mediod for VX. The very low equilibrium viqior pressure of VX (0.00063 mm Hg 2S C) (19) prevented reproducible transfer of VX fixim the penetration cell to die MINICAMS detection system. Thus, die only quantitative mechanical module in the DTN for VX is the HS-GC/MS test for VX liquid. Four nanomaterials passed this test (Figure 4). The high correlation of the nanomaterials that passed the HS-GC/MS tests for all diree CWAs (HD, GD, and VX), as well as die penetration cell test for HD and GD, indicates the universal ability of these materials to neutralize both vesicants and nerve agents. 

Response time is defined as the minimum time required to obtain a positive, reproducible response at the Limit of Detection and at a very high concentration that is approximately equivalent to an Ect5o [1] for severe human effects by vapor inhalation of agents (10 to 50 mg-min/m for nerve agents and 100 mg-min/m for blister agents). 

The development of the M43A1 eliminated the need for solution preparation. This device also provided faster and more reproducible responses to less than the IDLH level concentration of nerve agents. The M43A1, however, does not have HD detection capability. 

Relatively few PBPK models have been developed to describe the pharmacokinetics and pharmacodynamics of chemical warfare nerve agents. Maxwell et aV developed a PBPK-PD model for GD in the rat, describing the inhibition of AChE and carboxylesterase (CaE) in blood and tissues with mass balance equations based on parameters for blood flow, tissue volumes, GD metabolism and tissue/plasma partition coefficients. The resulting model gives accurate predictions of AChE activity in the blood and seven different tissues following intramuscular dosing with 90 pg GD kg bodyweight (BW), and was able to reproduce dose-response AChE inhibition from 10 to 100% in the brain. 

Figure 11. 22 Colorimetric detection of nerve gas agents by oximate formation. The spectra show the progress of the reaction by the disappearance of ther /r —> tt band at 461 nm and the appearance of the product absorption at 413 nm through an isosbestic point indicating clean conversion (reproduced by permission of The Royal Society of Chemistry).

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