Аннотация:Organophosphorus nerve agents (OPNAs) are highly toxic compounds that were originally developed as strong pesticides in the 1930s. Since then, a large number of OPNAs have been synthesized and accumulated for military purposes. Despite the fact that the use of these substances is prohibited by the Convention on the Prohibition of Chemical Weapons [1] and their stocks are being systematically destroyed, there are still concerns that the OPNAs can be used for terrorist purposes. As part of this activity, the search for new biomarkers that can reliably establish evidence of the use of nerve agents on human is relevant.
As part of these tests, an approach for the extraction of modified tripeptide CH3P(O)(OCH2(CH3)CH3)-Tyr-Thr-Lys(OH) (Y*TK) from human blood plasma, artificially exposed to sarin was developed. Mass spectrometric properties of the modified Y * TK tripeptide, including fragmentation pathways, were studied with use of electrospray ionization and high-resolution tandem mass spectrometry for the subsequent development of an alternative method of the detection of sarin albumin adduct during retrospective monitoring of human blood samples. For these purposes, the tripeptide Y * TK and the isotope labeled tripeptide Y * TK CD3 were synthesized and analyzed. This approach has been successfully used in combination with the subsequent determination of Y * TK by liquid chromatography and high resolution tandem mass spectrometry.
For the separation of Y * TK tripeptide by the reversed-phase HPLC-MS/MS, optimal conditions were chosen, allowing the rapid detection of this analyte in human plasma at the level of 0.5 ng / mL and higher.
This work was supported by the Russian Science Foundation (Grant No. 19-13-00057) for Lomonosov Moscow State University.
[1] Convention on the Prohibition of the Development, Production, Stockpiling and Use of Chemical Weapons and on their Destruction, Technical Secretariat of the Organisation for Prohibition of Chemical Weapons, The Hague, 1997, accessible through internet http: / /www.opcw.org.
