Examination of Firearms Review: 2007 to 2010 - Interpol

Other methods to detect organophosphorus nerve agents exposure consist of
refluoridation of nerve agents adducted to the butyrylcholinesterase prior to
solid-phase extraction and analysis by isotope-dilution gas chromatographymass
spectrometry, 53 or by analysis of the dialkylphosphates metabolites
found in urine by GC-MS/MS. 54 The fluoride ion-based regeneration method
has been used successfully in a number of cases. For example, it allowed the
quantification of VX-butyrylcholinesterase adduct in plasma, resulting from a
relatively low-level accidental human exposure case, by gas chromatographyhigh
resolution mass spectrometry of the resulting biomarker ethyl
methylphosphonofluoridate (VX-G), 55 or by GC-MS/MS of VX-G in red blood
cells. 56 The same method was applied to the detection of VX-G in Gottingen
minipig red blood cells after whole-body exposure to VX vapour, 57 while VX in
plasma could be identified directly. 58
The fluoride method was also applied to analysis of soman in rat plasma. 59
The relative toxicity of the four soman stereoisomers was also investigated. 60
A new method, based on high-performance liquid chromatography-mass
spectrometry with negative ion electrospray ionisation and time-of-flight
detection (LC-ESI-MS-TOF), has been developed and validated for the
determination of isopropyl methylphosphonic acid (IMPA) and cyclohexyl
methylphosphonic acid (CMPA), the metabolic hydrolysis products of sarin,
and cyclosarin, respectively. 61
A lab-on-a-chip method has been developed for the detection of sarin in
blood, based on continuous-flow microfluidics with sequential stages for lysis
of whole blood, regeneration of free nerve agent from its complex with blood
cholinesterase, protein precipitation, filtration, enzyme-assisted reaction, and
optical detection. 62
Exposures to vesicants such as sulphur mustard (HD) or nitrogen mustard
(HN) can also be determined by metabolites analysis. For example, exposure
to HD can be ascertained by measuring thiodiglycol (TDG), TDG-sulphoxide,
and the bis-mercapturate of mustard sulphone in urine. 63 Other metabolites
such as adducts of HD with albumin, with glutamic and aspartic acids of
plasma proteins or with haemoglobin have also been extensively
studied, 64,65,66 while detection of blood protein adducts can be identified from
the cleavage of protein-hydroxyethylthioethyl esters to produce thiodiglycol. 67
The albumin-derived adduct biomarkers present in blood samples have also
been investigated for nitrogen mustards (HN-1, HN-2, and HN-3). 68
The determination of the sesqui-mustard metabolites bis(2hydroxyethylthio)alkanes
(n = 1-5) and the oxy-mustard metabolite bis(2hydroxyethylthioethyl)ether
in human urine by HPLC-MS/MS could similarly
provide indication of exposure to sesqui- and oxy-mustards that are potential
chemical weapons because of their vesicant properties. 69
534