Monitoring Sulfur Mustard Exposure by Gas Chromatography-Mass Spectrometry Analysis of Thiodiglycol Cleaved From Blood Proteins
Abstract
A gas chromatography-mass spectrometry method for determining exposure to the chemical warfare agent 2,2'-dichlorndiethyl sulfide (sulfur mustard; HD) has been developed. The technique is based upon quantitating thiodiglycol (TDG) released from blood protein adducts that are formed upon exposure to HD. Protein was precipitated from plasma, whole blood, or packed red blood cells (RBCs) and then treated with sodium hydroxide to liberate protein-bound TDG. The TDG was derivatized with pentafluorobenzoyl chloride that enabled sensitive detection by negative-ion chemical ionization. Octadeuterothiodiglycol was used as an internal standard. Exposure of human plasma to HD (25nM to 4OOnM) resulted in a linear relationship (r2 = 0.9995) between HD concentration and released TDG levels with means ranging from 2.0 to 38 pg/mg protein. The coefficients of variation expressed as a percentage for the data points ranged from 2 to 11.5%. The application of this procedure was demonstrated in two HD animal exposure models. African green monkeys (Chiorocebus aethiops) were exposed intravenously to 1 mg/kg HD, and TDG levels in blood samples were analyzed out to 45 days post-exposure. Mean TDG levels were determined to be 220 pg/mg protein on day 1 and declined to 10 pg/mg protein on day 45. Yorkshire cross pigs (Sus scrofa) were cutaneously exposed to neat liquid HD, and TDG levels in plasma were determined out to 21 days following exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA442473
Entities
People
- Benedict R. Capacio
- Dana R. Anderson
- Gennady E. Platoff
- John S. Graham
- Joseph P. Smith
- Michael T. Delion
- William D. Korte
Organizations
- United States Army Medical Research Institute of Chemical Defense