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 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 > or = 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 > or = 0.1 microM 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.
Fidder
A
A
Department of Chemical Toxicology, TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.
Noort
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D
de Jong
A L
AL
Trap
H C
HC
de Jong
L P
LP
Benschop
H P
HP
D000478:Alkylation; D000818:Animals; D002619:Chemical Warfare Agents / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects*; D005466:Fluorocarbons / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D006454:Hemoglobins / Q000032:analysis / Q000737:chemistry / Q000187:drug effects*; D007202:Indicators and Reagents / Q000737:chemistry; D007275:Injections, Intravenous; D017879:Isothiocyanates; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009151:Mustard Gas / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D013056:Spectrophotometry, Ultraviolet; D013462:Sulfur Radioisotopes; D013861:Thiocyanates / Q000737:chemistry; D014633:Valine / Q000737:chemistry*; D005464:Fluorobenzenes
D002619:Chemical Warfare Agents; D005466:Fluorocarbons; D006454:Hemoglobins; D007202:Indicators and Reagents; D017879:Isothiocyanates; D009151:Mustard Gas; D013462:Sulfur Radioisotopes; D013861:Thiocyanates; D014633:Valine; C007924:heptafluorobutyric anhydride; C003064:pentafluorophenylisothiocyanate; D005464:Fluorobenzenes