A High-Throughput UHPLC-MS/MS Method for the Quantification of Five Aged Butyrylcholinesterase Biomarkers from Human Exposure to Organophosphorus Nerve Agents

Details

• Alternative Title:
  Biomed Chromatogr
• Personal Author:
  Graham, Leigh Ann ; Johnson, Darryl ; Carter, Melissa D. ; Stout, Emily G. ; Erol, Huseyin A. ; Isenberg, Samantha L. ; Mathews, Thomas P. ; Thomas, Jerry D. ; Johnson, Rudolph C.
• Description:
  Organophosphorus nerve agents (OPNAs) are toxic compounds that are classified as prohibited Schedule 1 chemical weapons. In the body, OPNAs bind to butyrylcholinesterase (BChE) to form nerve agent adducts (OPNA-BChE). OPNA-BChE adducts can provide a reliable, long-term protein biomarker for assessing human exposure. A major challenge facing OPNA-BChE detection is hydrolysis (aging), which can continue to occur after a clinical specimen has been collected. During aging, the o-alkyl phosphoester bond hydrolyzes, and the specific identity of the nerve agent is lost. To better identify OPNA exposure events, a high-throughput method for the detection of five aged OPNA-BChE adducts was developed. This is the first diagnostic panel to allow for the simultaneous quantification of any Chemical Weapons Convention Schedule 1 OPNA by measuring the aged adducts methyl phosphonate, ethyl phosphonate, propyl phosphonate, ethyl phosphoryl, phosphoryl and unadducted BChE. The calibration range for all analytes is 2.00-250. ng/mL, which is consistent with similar methodologies used to detect unaged OPNA-BChE adducts. Each analytical run is 3 min, making the time to first unknown results, including calibration curve and quality controls, less than 1 h. Analysis of commercially purchased individual serum samples demonstrated no potential interferences with detection of aged OPNA-BChE adducts, and quantitative measurements of endogenous levels of BChE were similar to those previously reported in other OPNA-BChE adduct assays.
• Subjects:
  • Biomarkers
  • Butyrylcholinesterase
  • Chromatography, Liquid
  • Environmental Exposure
  • Half-Life
  • High-Throughput Screening Assays
  • Humans
  • Nerve Agents
  • Organophosphorus Compounds
  • Tandem Mass Spectrometry
• Source:
  Biomed Chromatogr. 31(4).
• Pubmed ID:
  27572107
• Pubmed Central ID:
  PMC5713885
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States
• Volume:
  31
• Issue:
  4
• Download URL:
  https://stacks.cdc.gov/view/cdc/50472/cdc_50472_DS1.pdf
• File Type:
  [PDF - 1.16 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e5705d6d082a36d71b454a5a0ea82d038930d1322d9d4f860094d6747780abf1