A quantitative method to detect human exposure to sulfur and nitrogen mustards via protein adducts

Details

• Journal Article:
  J Chromatogr B Analyt Technol Biomed Life Sci
• Personal Author:
  Pantazides, Brooke G. ; Quiñones-González, Jennifer ; Rivera Nazario, Danisha M. ; Crow, Brian S. ; Perez, Jonas W. ; Blake, Thomas A. ; Johnson, Rudolph C.
• Description:
  Sulfur and nitrogen mustards are internationally banned vesicants listed as Schedule 1 chemical agents in the Chemical Weapons Convention. These compounds are highly reactive electrophiles that form stable adducts to a variety of available amino acid residues on proteins upon exposure. We present a quantitative exposure assay that simultaneously measures agent specific protein adducts to cysteine for sulfur mustard (HD) and three nitrogen mustards (HN1, HN2, and HN3). Proteinase K was added to a serum or plasma sample to digest protein adducts and form the target analyte, the blister agent bound to the tripeptide cysteine-proline-phenylalanine (CPF). The mustard adducted-tripeptide was purified by solid phase extraction and analyzed using isotope dilution LC-MS/MS. Product ion structures were identified using high-resolution product ion scan data for HD-CPF, HN1-CPF, HN2-CPF, and HN3-CPF. Thorough matrix comparison, analyte recovery, ruggedness, and stability studies were incorporated during method validation to produce a robust method. The method demonstrated long term-stability, precision (RSD < 15%), and intra- and inter-day accuracies > 85% across the reportable range of 3.00-200 ng/mL for each analyte. Compared to previously published assays, this method quantitates both sulfur and nitrogen mustard exposure biomarkers, requires only 10 μL of sample volume, and can use either a liquid sample or dried sample spot.
• Subjects:
  • Article
  • Sulfur mustard
  • Nitrogen mustard
  • Protein biomarker
  • Cysteine adducts
  • LC-MS/MS
  • Quantitative method
  • Biomarkers
  • Chromatography, High Pressure Liquid
  • Cysteine
  More +
• Source:
  J Chromatogr B Analyt Technol Biomed Life Sci. 1121:9-17
• Pubmed ID:
  31082684
• Pubmed Central ID:
  PMC8054111
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHS/United States
• Volume:
  1121
• Download URL:
  https://stacks.cdc.gov/view/cdc/105644/cdc_105644_DS1.pdf
• File Type:
  [PDF - 1.11 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:77ab6ff031c74527ee0f945840f70f92a62cd3546e51da675898c431c2c309238a4251a041604e55c70f1419ef1a717d8976472891b2c25cd87a7a94d85db83c