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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 32, Number 1, January/February,
pp.37-43
Gas Chromatographic–Mass Spectrometric
Analysis of Sulfur Mustard-Plasma Protein Adducts: Validation
and Use in a Rat Inhalation Model
Benedict R. Capacio, J. Richard Smith,
Richard J. Lawrence, Brian L. Boyd, Alicia M. Witriol, Michele
L. Conti, Jennifer L. Collins, and Alfred M. Sciuto
Analytical Toxicology Division, U.S. Army Medical Research
Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen
Proving Ground, Maryland 21010-5400
Sulfur mustard (HD) is an alkylating agent that
reacts rapidly with macromolecular targets resulting in the formation
of stable adducts providing depots for markers of exposure. The
purpose of this study was to validate an analytical procedure
for detection of HD-plasma protein adducts and to establish the
utility of the method in an HD rat inhalation study. Calibration
curves were prepared in human and rat plasma at six levels of
HD (12.5 to 400nM). Correlation coefficients for the mean data
were 0.9987 for human and 0.9992 for rat plasma. The percent
coefficient of variation (%CV) derived from the mean concentration
data ranged from 0.53 to 14.1% in human (n = 5) and 0.57 to 10.63%
in rat (n = 6) plasma. Intraday and interday precision and accuracy
studies were conducted at three concentration levels (25, 150,
300nM) to represent low, medium, and high concentrations of HD
relative to those employed in the calibration curve. Precision
and accuracy were assessed by determining %CV and % error, respectively.
For intra- and interday studies, the %CVs and absolute % errors
were less than 15%. The limits of quantitation were 20.88nM for
human and 16.73nM for rat plasma. In animal studies, rats received
nebulized HD at six doses. The data indicate a dose-dependent
relationship between maximal plasma concentrations and dose administered
(R2 = 0.9728). Results from this study indicate an accurate,
precise, and sensitive method. The method was useful in determining
plasma protein adduct formation in a rat inhalation model.
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