Investigation of sarin(Se) reactivity against human plasma proteins using liquid chromatography-tandem mass spectrometry

J Mass Spectrom. 2018 Feb;53(2):138-145. doi: 10.1002/jms.4045.

Abstract

Electron ionization mass spectrum of sarin(Se) was interpreted in compare of sarin MS spectrum. Inhibition of butyrylcholinesterase of human plasma by sarin and sarin(Se) was determined spectrophotometrically using modified Ellman method. It appeared that after incubation with sarin and sarin(Se), cholinesterase inhibition were 93% and 83%, respectively. Sarin, sarin(Se), and sarin(Se)-d7 were spiked into a vial containing human plasma, and albumin adduct metabolites were identified using liquid chromatography-tandem mass spectrometry. The experiments show that these agents are attached to tyrosine on albumin in human blood. Corresponding deuterated adducts were used to confirm the proposed mechanisms for the formation of the fragments in mass spectrometry experiments.

Keywords: acetylcholinesterase; adduct metabolites; liquid chromatography-tandem mass spectrometry; sarin; sarin(Se).

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Blood Proteins / chemistry*
  • Blood Proteins / metabolism
  • Butyrylcholinesterase / metabolism
  • Chemical Warfare Agents / chemistry*
  • Chemical Warfare Agents / metabolism
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / metabolism
  • Chromatography, High Pressure Liquid
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Organoselenium Compounds / chemistry*
  • Protein Binding
  • Sarin / chemistry*
  • Tandem Mass Spectrometry
  • Tyrosine / chemistry

Substances

  • Blood Proteins
  • Chemical Warfare Agents
  • Cholinesterase Inhibitors
  • Organoselenium Compounds
  • Tyrosine
  • Sarin
  • Butyrylcholinesterase