MSACL 2019 EU Abstract

Determination of Biomarkers of Organophosphorus Agent Intoxication by Ion Chromatography and Tandem Mass Spectrometry

Timur Baygildiev, Mikhail Vokuev, Roman Ogorodnikov, Arcady Braun, Igor Rybalchenko, Igor Rodin
Lomonosov Moscow State University

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Igor Rodin (Presenter) Lomonosov Moscow State University >> POSTER (PDF)

Presenter Bio: Igor Rodin has completed his PhD in 2009 in Lomonosov Moscow State University, Russia and has attained habilitation in 2017 in the same University.
Head of chromatography mass-spectrometry laboratory in Analytical Chemistry Division and full professor (at part time) in Physical Chemistry Division of Chemistry department in Lomonosov Moscow State University, Russia.
Member of Scientific Boards of Russian Mass-Spectrometry Society and Association ofChemical Toxicological and Forensic Chemical Specialists (Russia)
Area of interest: chromatography and mass spectrometry methods and assays development for biomedical, forensic and environmental applications.

Relevant Financial Disclosures (within past 24 months) Grant/Research Support Russian Science Foundation Conflict mitigation NOT REQUIRED.

Introduction
Organophosphorus nerve agents (ONAs) are one of the most toxic compounds that have been applied several times during military clashes and terrorist attacks. In this regard, it is very important to improve and simplify the existing methods for the determination of ONAs intoxication. Timely determination of ONAs markers in people’s urine can save their lives or indicate the degree of exposure to toxic substances. Low molecular weight biomarkers of ONAs are methylphosphonic acid (MPA) and alkyl methylphosphonic acids (AMPAs). MPA is the most stable and long-lived marker of ONAs, however, its detection does not allow to establish the specific type of agent used. AMPAs are less stable, but they can serve as biomarkers of a certain type of ONAs.

Objectives
The aim of the research was to develop a universal approach for the simultaneous accurate determination of the wide range of polar (MPA, EMPA, APAs) and moderately polar nerve agent markers (AMPAs) in urine.

Methods
Ion chromatography (IC) with tandem mass-spectrometry (MS/MS) using ion-exchange solid-phase extraction (SPE), self-made PS-DVB-based anion-exchanger as stationary phase and deuterated internal standards.

Results
For the determination of wide range of alkylphosphonic acids and alkyl methylphosphonic acids in urine, simple and universal IC-MS/MS approach was developed and fully validated. The study of analyte retention on the in house made PS/DVB-based anion-exchange column showed that APAs are mainly retained due to ionic interaction, and AMPAs due to hydrophobic interactions, which allows simultaneous determination of both highly polar compounds and compounds with two different MS instruments and successfully tested on the urine samples from the Biomedical hydrophobic fragments. The developed sample preparation procedure using anion-exchange cartridges for solid-phase extraction provides a high recovery values of analytes and is ideally combined with the further anion-exchange separation. Application of deuterated internal standards and tandem mass spectrometry led to the high reliability, accuracy and sensitivity of APAs and AMPAs determination in urine. To increase reliability, the proposed procedure was validated on Organization for the Prohibition of Chemical Weapons Biomedical Proficiency Test.

Conclusion
Simultaneous determination of APAs and AMPAs allows not only to reveal the fact of organophosphorus agent intoxication, but to establish its type and sometimes origin. From our point of view, the developed IC-MS/MS approach is the most appropriate way to determine a wide range of phosphonic acids without the use of derivatization.

Aknowledgements
This work was supported by the Russian Science Foundation (Grant No. 19-13-00057) for Lomonosov Moscow State University.