AI Article Synopsis

  • Highly toxic organophosphorous nerve agents (OPAs) like VX, GB, and GF have been implicated in recent conflicts and terror attacks, highlighting the need for effective detection methods.
  • A novel technique was developed for detecting alkyl methylphosphonic acid (AMPA) metabolites in urine, utilizing two solid phase extraction cartridges for improved sensitivity and selectivity in identifying nerve agent biomarkers.
  • The method demonstrated high sensitivity with limits of quantitation between 10-100 pg/mL and successful in vivo application, achieving the detection of the IMPA metabolite in rabbit urine for up to 15 days post-exposure, making it one of the most efficient methods available.

Article Abstract

Highly toxic organophosphorous nerve agents (OPAs) have been used in several armed conflicts and terror attacks in the last few decades. A new method for retrospective determination of alkyl methylphosphonic acid (AMPA) metabolites in urine after exposure to VX, GB and GF nerve agents was developed. This method enables a rapid, sensitive and selective determination of trace levels of the nerve agent biomarkers ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA) and cyclohexyl methylphosphonic acid (CMPA) in urine. The new technique involves a unique combination of two solid phase extraction (SPE) cartridges: a Ba/Ag/H cartridge for urine interference removal, and a ZrO cartridge for selective reconstitution and enrichment of the AMPAs. Extraction of AMPAs from the ZrO cartridge was accomplished with a 1% ammonium hydroxide (NHOH) solution and was followed by analysis via liquid chromatography-mass spectrometry (LC-MS). The limits of quantitation (LOQs) were in the range of 10-100 pg/mL with recoveries of 64-71% (± 5-19%) after fast sample preparation and a total LC-MS analysis cycle time of 15 min and 13 min, respectively. This method was successfully applied in vivo in a rabbit that was exposed to 0.5 LD (7.5 µg/kg, i.v.) sarin for retrospective monitoring of the IMPA metabolite in urine. For the first time, IMPA was determined in rabbit urine samples for 15 days post-exposure, which is longer than any reported post-exposure method for AMPAs. To the best of our knowledge, this new method is the most sensitive and rapid for AMPA determination in urine by LC-MS/MS analysis.

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http://dx.doi.org/10.1007/s00204-020-02827-xDOI Listing

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