New high-performance liquid chromatography tandem mass spectrometry technique based on derivatization for the determination of nerve agents intoxication biomarkersтезисы докладаЭлектронная публикацияТезисы
Аннотация:Sarin, soman, VX, and VR are the most common representatives of the extremely dangerous and toxic class of nerve agents. In the environment and in humans or animals, these compounds hydrolyze rapidly to form isopropyl (iPMP), pinacolyl (PMP), ethyl (EMP) and isobutyl (iBMP) methylphosphonates, respectively. Subsequently, all alkyl methylphosphonates (AMP) are quite quickly converted into the final hydrolysis product, methylphosphonic acid (MPA). MPA is the most stable and long-lived marker of nerve agents, however, its determination does not allow to establish the specific type of chemical agent used. Alkyl methylphosphonates are less stable, but they can serve as markers for the use of a particular type of nerve agent, that may allow to determine the origin of the nerve agent used. Other important analogies of MPA are ethyl (EPA) and propylphosphonic acid (PPA), which may serve as a marker of novel nerve agents of the second generation. Thus, to establish reliably the fact of using nerve agents, it is necessary to develop a technique for the simultaneous determination of alkyl phosphonic acids (APA) and AMP, which is not an easy task as these substances are very polar and have low retention on the reversed phase columns. We developed an approach for the simultaneous determination of APA and AMP using a combination of derivatization and reversed phase HPLC-MS/MS. For the derivatization p-methoxyphenacyl bromide was proposed. This agent may react with both APA, yielding mainly products by the two groups and AMP. For the optimization of the reaction conditions, appropriate amounts of agent and catalyst, suitable values of time and temperature of the reaction were found. LC separation of the derivates was performed in the gradient elution mode. It was found that simultaneous MS detection of APA and AMP may be carried out only in the positive ESI mode. Very low detection limits (less than 1 ng/ mL) for most of APA and AMP were achieved in the multiple reaction monitoring modes. The developed approach was applied to the environmental and biological samples. This work was supported by the Russian Foundation for Basic Research (Grant No. 18-33-20068 mol_a_ved).