Quantitative analysis of O-isopropyl methylphosphonic acid in serum samples of Japanese citizens allegedly exposed to sarin: Estimation of internal dosage
article
A convenient and rapid micro-anion exchange liquid chromatography (LC) tandem electrospray mass spectrometry (MS) procedure was developed for quantitative analysis in serum of O-isopropyl methylphosphonic acid (IMPA), the hydrolysis product of the nerve agent sarin. The mass spectrometric procedure involves negative or positive ion electrospray ionization and multiple reaction monitoring (MRM) detection. The method could be successfully applied to the analysis of serum samples from victims of the Tokyo subway attack and of an earlier incident at Matsumoto, Japan. IMPA levels ranging from 2 to 135 ng/ml were found. High levels of IMPA appear to correlate with low levels of residual butyrylcholinesterase activity in the samples and vice versa. Based on our analyses, the internal and exposure doses of the victims were estimated. In several cases, the doses appeared to be substantially higher than the assumed lethal doses in man.
Topics
Chemical warfare agentsLC tandem MSMultiple reaction monitoringO-isopropyl methylphosphonic acidSarinCholinesteraseFluoride ionMethylphosphonic acidO isopropyl metylphosphonic acidSarinUnclassified drugAnion exchange chromatographyArticleBlood levelChemical structureChemical warfareDiagnostic valueEnzyme activityEnzyme bindingEnzyme inhibitionHumanHydrolysisJapanLethal doseMethodologyPopulation exposurePriority journalTandem mass spectrometryToxicity testingButyrylcholinesteraseChemistry, AnalyticalChromatography, LiquidEnvironmental ExposureFemaleHumansMaleMass SpectrometryMolecular StructureOrganophosphorus CompoundsButyrylcholinesterase, EC 3.1.1.-Isopropyl methylphosphonic acid, 1832-54-8Organophosphorus CompoundsSarin, 107-44-8
TNO Identifier
234683
ISSN
0340-5761
Source
Archives of Toxicology, 72(10), pp. 671-675.
Pages
671-675
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