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Интеллектуальная Система Тематического Исследования НАукометрических данных |
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The development, production, stockpiling and use of chemical weapons are prohibited under the Chemical Weapons Convention1. In cases of alleged use of chemical warfare (CW) agents, environmental samples may be collected and analyzed for agents and their degradation products presented as a supporting evidence of a CW attack. Biomedical samples, e.g. blood and urine, may be analyzed for biological markers of poisoning as evidence that individuals have been exposed to a CW agent 2. Biomedical sample analysis also has applications in exposure monitoring, e.g. in individuals engaged in demilitarization activities, and for the diagnosis of poisoning prior to the administration of medical countermeasures. Lewisite [dichloro(2-chlorovinyl)arsine], a highly toxic chemical warfare agent with vesicant properties, was developed during World War I. Lewisite irritates the skin and eyes and is also poisonous when inhaled; but its clinical effects appear within seconds of exposure. Lewisite is very reactive; in aqueous media, it rapidly hydrolyzes to a stable water soluble derivative, 2-chlorovinylarsonous acid (CVAA), which is also toxic3. Several analytical methods have measured CVAA to determine lewisite exposure, etc. the authors4 determined CVAA in urine by using GC-MS for the 1,3-propanedithiol derivative. Several methods, based on the detection of CVAA, have been reported for the identification of lewisite in environmental5 and biological6 samples. These approaches have advantages but may require derivatization that add to sample preparation time. The main purpose of our work was to develop a rapid, sensitive technique for CVAA determination in urine samples. We present a method for the detection of CVAA in human and rat urines spiked with CVAA that is based on the materials used by liquid chromatography interfaced to negative ion-electrospray ionization-tandem mass spectrometry. Columns under gradient conditions were used. By automating and optimizing several sample cleanup steps, the method provides the LC–MS/MS instrument with sufficiently clean concentrated samples, at a rate comparable to that at which it quantifies them. The use of fast, automated sample preparation steps, employing separate solid-phase extraction analyte isolation, provides samples that are sufficiently clean and the 1 ng/ml limit of detection to be achieved. Thus, the method is well suited for the purpose of the biomonitoring of lewisite exposure in the event of a mass-casualty terrorist incident or in case of an accident at CW storage units characterized by high sample loads and the low concentrations to be detected. References 1- Convention on the Prohibition of the Development. Production. Stockpiling and Use of Chemical Weapons and on their Destruction. Technical Secretariat for the Organization for the Prohibition of Chemical Weapons. The Hague. 1997. 2- T.P. Logan, J.R. Smith, E.M. Jakubowski, R.E. Nielson, Toxicol. Methods 9 (1999) 275. 3- W.A. Waters, J.H. Williams, J. Chem. Soc. (1950) 18. 4- J.V.Wooten, D.L. Ashley, and A.M. Calafat, J. Chromatogr. B 772 (2002) 142. 5- B. Szostek, J.H. Aldstadt, J. Chromatogr. A 807 (1998) 253. 6- A. Fidder, D. Noort, A.G. Hulst, L.P.A. de Jong, H.P. Benschop, Arch. Toxicol. 74 (2000) 207.