Fluoride reactivation-enabled sensitive quantification of tabun adducts on human serum albumin by GC-MS/MS via isotope dilution

Bioanalysis. 2019 Dec;11(23):2145-2159. doi: 10.4155/bio-2019-0161. Epub 2019 Nov 15.

Abstract

Organophosphorus nerve agents inhibit the cholinesterase activity by phosphylation of the active site serine. The resulting phosphylated cholinesterase and adducts on human serum albumin (HSA) are appropriate biomarkers for nerve agents exposure. Several methods have been developed for the detection of nerve agents, including fluoride reactivation or alkaline cleavage. It was previously thought that some nerve agents adducts to HSA could not be detected via fluoride regeneration. In our study, the results showed that tabun (GA) adducts of HSA could be detected by fluoride regeneration. The sample preparation included acetone precipitation, washing and SPE. Deuterated tabun (d5-GA) was applied as the internal standard. The product of regenerated fluorotabun is detected with a good linearity (R2 > 0.997) in the concentration range from 0.02 to 100.0 ng/ml, small relative standard deviation (≤6.89%) and favorable recoveries between 94.8 and 106.3%. The established preparation confirmed the fluorotabun was regenerated from the GA-HSA adducts.

Keywords: GC–MS/MS; HSA adducts; acetone precipitation; fluoride reactivation; isotope dilution; tabun.

MeSH terms

  • Chromatography, Gas
  • Fluorides / chemistry*
  • Humans
  • Indicator Dilution Techniques*
  • Molecular Structure
  • Organophosphates / analysis*
  • Serum Albumin, Human / chemistry*
  • Tandem Mass Spectrometry

Substances

  • Organophosphates
  • Fluorides
  • tabun
  • Serum Albumin, Human