Monitoring of in Vitro and in Vivo Exposure to Sulfur Mustard by GC/MS Determination of the N-Terminal Valine Adduct in Hemoglobin after a Modified Edman Degradation

We report that exposure to the chemical warfare agent sulfur mustard can be monitored by means of a modified Edman degradation involving selective release of the N-terminal valine adduct of hemoglobin with the agent. The degree of alkylation of the N-terminal valine in human hemoglobin is approximat...

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Bibliographic Details
Published in:Chemical research in toxicology 1996-06, Vol.9 (4), p.788-792
Main Authors: Fidder, Alex, Noort, Daan, de Jong, Ad L, Trap, Hendrik C, de Jong, Leo P. A, Benschop, Hendrik P
Format: Article
Language:English
Subjects:
Alkylation
Animals
Chemical Warfare Agents - analysis
Chemical Warfare Agents - chemistry
Chemical Warfare Agents - toxicity
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Erythrocytes - chemistry
Erythrocytes - drug effects
Fluorocarbons - chemistry
Gas Chromatography-Mass Spectrometry
Guinea Pigs
Hemoglobins - analysis
Hemoglobins - chemistry
Hemoglobins - drug effects
Indicators and Reagents - chemistry
Injections, Intravenous
Isothiocyanates
Magnetic Resonance Spectroscopy
Male
Mustard Gas - administration & dosage
Mustard Gas - analysis
Mustard Gas - chemistry
Mustard Gas - toxicity
Spectrophotometry, Ultraviolet
Sulfur Radioisotopes
Thiocyanates - chemistry
Valine - chemistry
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Summary:We report that exposure to the chemical warfare agent sulfur mustard can be monitored by means of a modified Edman degradation involving selective release of the N-terminal valine adduct of hemoglobin with the agent. The degree of alkylation of the N-terminal valine in human hemoglobin is approximately 1−2% of the total alkylation induced in hemoglobin upon treatment of human blood with sulfur mustard. After modified Edman degradation, followed by derivatization with heptafluorobutyric anhydride, the obtained pentafluorophenyl thiohydantion derivative of the valine adduct could be analyzed at a ≥0.5 fmol level by means of GC/MS under negative ion chemical ionization conditions. Applying this procedure, in vitro exposure of human blood to ≥0.1 μM of sulfur mustard could be determined. In vivo exposure of guinea pigs could also be established at 48 h after intoxication intravenously with 0.5 mg/kg (0.06 LD50) of the agent.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx9502150