Integrating Effect-Directed Analysis and Chemically Indicative Mass Spectral Fragmentation to Screen for Toxic Organophosphorus Compounds

Dan Loewenthal, Department of Analytical Chemistry, Israel Institute for Biological Research, Ness Ziona, Israel (dan.loewenthal@chem.ox.ac.uk)
Shai Dagan, Department Of Analytical Chemistry, Israel Institute For Biological Research, Ness Ziona, Israel
Eyal Drug, Department Of Analytical Chemistry, Israel Institute For Biological Research, Ness Ziona, Israel

Analytical chemists are often challenged to screen for bioactive compounds in complex matrices, sometimes without a-priori knowledge of the exact compound of interest. Therefore, “flagging” techniques, highlighting common characteristics of bioactive compounds, are highly sought after. In this work, we demonstrate a double “flagging” method, where unknown organophosphorus acetylcholinesterase inhibitors are “flagged” out of a complex matrix by the presence of a phosphorus atom as well as their acetylcholinesterase inhibition. This is accomplished by “flagging” the LC chromatographic retention time of phosphorus-indicative ions using accurate mass high energy in-source CID products, and the retention time of acetylcholinesterase inhibiting compounds using a parallel micro-fractionation-based bioassay. We successfully apply this method to screen VX, VM, and RVX nerve agents as well as methomyl, a carbamate pesticide, out of soil and whole blood samples at low μM to sub-μM concentrations.  This methodology can be easily extended to diverse chemical families and biological activities of interest. 

 

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Short Biography of Presenting Author

2022 - Present - PhD Student, Physical Chemistry (University of Oxford, Kukura group - mass photometry)

2020 - 2022 - M.Sc, Physical Chemistry (Tel Aviv University, Bisker group - single-walled carbon nanotube fluorescent sensors, magna cum laude)

2018 - 2022 - Israel Institute for Biological Research (Department of Analytical Chemistry - small molecule mass spectrometry)

2014 - 2018 - B.Sc, Natural Science (Israel Open University)

 Awards

Clarendon Scholarship (Oxford University, 2022)
Lincoln Kingsgate Scholarship (Lincoln College - Oxford University, 2022)
Best Poster (Analytical and Bioanalytical Chemistry Conference, 2020)