Determination of VX-G Analogue in Red Blood Cells via Gas Chromatography-Tandem Mass Spectrometry Following an Accidental Exposure to VX

Abstract

A sensitive method for determining exposure to the chemical warfare agent VX is described in which the biomarker ethyl methylphosphonofluoridate (VX-G) is measured in red blood cells (RBCs) following treatment with fluoride ion using isotope-dilution gas chromatography-tandem mass spectrometry. The analyte was isolated via solid-phase extraction and detected using ammonia chemical ionization in the multiple reaction monitoring mode. A good linear relationship was obtained in the quantitative concentration range of 4 ng/mL to 1000 ng/mL with an absolute detection limit of < 1 pg on column. The method has been applied to the analysis of RBCs from a laboratory worker accidentally exposed to VX vapor. Detection and quantitation of VX-G were possible in samples taken as late as 27 days following exposure.

Analytical approaches for monitoring exposure to organophosphorus and carbamate agents through analysis of protein adducts

“…Results were reported by Solano et al [46] and by McGuire et al [49] Solano worked with serum using a slight modification of the Adams method (0.25 M potassium fluoride vs 0.7 M). Results were reported by Solano et al [46] and by McGuire et al [49] Solano worked with serum using a slight modification of the Adams method (0.25 M potassium fluoride vs 0.7 M).…”

“…[24] Proteins that have been used for detection of exposure to organophosphylates are butyrylcholinesterase, [22,40,[46][47][48] acetylcholinesterase, [21,49,50] and serum albumin. [24] Proteins that have been used for detection of exposure to organophosphylates are butyrylcholinesterase, [22,40,[46][47][48] acetylcholinesterase, [21,49,50] and serum albumin.…”

“…Analysis of protein biomarkers was adopted to improve retrospective detection of exposure to organophosphylates. [24] Proteins that have been used for detection of exposure to organophosphylates are butyrylcholinesterase, [22,40,[46][47][48] acetylcholinesterase, [21,49,50] and serum albumin. [45,51] For exposure to carbamates, only butyrylcholinesterase has been described.…”

Noncholinesterase Protein Targets of Organophosphorus Pesticides

“…The released VX was purified on solid-phase extraction cartridges and analyzed by gas chromatography mass spectrometry [59,60]. Plasma and red blood cells from the victim were treated with potassium fluoride to release VX from blood proteins.…”

History and perspectives of bioanalytical methods for chemical warfare agent detection

“…The fact that the method still works with soman suggests that fluoride may be displacing the MeP(O)OCH(Me)CMe 3 moiety from other adducts, probably tyrosine adducts on albumin or from carboxylesterases [80]. The method was applied successfully to casualties of the Matsumoto and Tokyo sarin attacks [37], and to an accidental exposure of a laboratory worker to VX [81]. An experimentally more demanding procedure applied to Japanese casualties liberated sarin residues from red blood cell AChE as isopropyl methylphosphonic acid, after sequential digestion with trypsin and alkaline phosphatase [82].…”