Biological fate of sulphur mustard: identification of valine and histidine adducts in haemoglobin from casualties of sulphur mustard poisoning.
1. Analytical methods were developed for the detection of N-terminal valine and histidine adducts in haemoglobin alkylated with sulphur mustard. 2. N-(2-hydroxyethylthioethyl)-N-terminal valine was selectively cleaved from globin with the Edman reagent pentafluorophenyl isothiocyanate. The resulting thiohydantoin derivative was analysed by high resolution gc-ms using negative ion chemical ionization. An alternative procedure, involving acid hydrolysis of globin to its constituent amino acids and conversion of the adduct to its di-TBDMS derivative, was less sensitive. 3. N-(2-hydroxyethylthioethyl)histidine was analysed, after acid hydrolysis of globin, as its fluorenylmethyloxycarbonyl derivative by lc-ms-ms using electrospray ionisation and selected reaction monitoring. 4. N-(2-hydroxyethylthioethyl)valine and (2-hydroxyethylthioethyl)histidine were detected in globin isolated from a rat treated percutaneously with sulphur mustard, and in globin from five blood samples collected from human casualties of sulphur mustard poisoning. The adducts are proposed as biological markers of sulphur mustard poisoning. in addition to urinary metabolites and DNA adducts.
Black
R M
RM
Protection and Life Science Division, Defence Evaluation and Research Agency, Porton Down, Salisbury, UK.
Clarke
R J
RJ
Harrison
J M
JM
Read
R W
RW
D000477:Alkylating Agents / Q000493:pharmacokinetics* / Q000506:poisoning; D000818:Animals; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics* / Q000506:poisoning; D006454:Hemoglobins / Q000737:chemistry*; D006639:Histidine / Q000031:analogs & derivatives / Q000737:chemistry*; D006801:Humans; D009151:Mustard Gas / Q000493:pharmacokinetics* / Q000506:poisoning; D051381:Rats; D014633:Valine / Q000031:analogs & derivatives / Q000737:chemistry*
D000477:Alkylating Agents; D002619:Chemical Warfare Agents; D006454:Hemoglobins; D006639:Histidine; D014633:Valine; D009151:Mustard Gas