| |
Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 32, Number 1, January/February,
pp.31-36
Improvements in the Methodology of Monitoring
Sulfur Mustard Exposure by Gas Chromatography– Mass Spectrometry
Analysis of Cleaved and Derivatized Blood Protein Adducts
Richard J. Lawrence[1], J. Richard Smith[1],
Brian L. Boyd[2], and Benedict R. Capacio[1]
[1]U.S. Army Medical Research Institute of Chemical Defense,
3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland
21010-5400 and
[2]Battelle Memorial Institute, Aberdeen Proving
Ground, Maryland 21010-5400
An analytical method for determining exposure
to 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD) has been
enhanced. The method is based on the cleavage of adducted HD
(protein-hydroxyethylthioethyl esters) to produce thiodiglycol.
Following cleavage, a deuterated internal standard is added,
and the analytes are extracted, derivatized, and analyzed by
gas chromatography–negative ion chemical ionization-mass
spectrometry. Inclusion of a concentration step, addition of
solid sodium bicarbonate to neutralize excess derivatization
reagent, and optimization of method and instrument conditions
provided dramatic increases in signal-to-noise ratio. A five-day
precision and accuracy study was conducted, including interday
and intraday unknown analysis. Linearity was verified by a R2 > 0.9995
for all five curves evaluated. The precision and accuracy of
the assay were demonstrated to be excellent by evaluation of
the interday and intraday unknown samples (< 10% relative
standard deviation and relative error in most cases). Statistical
treatment of the method blanks and calibration results demonstrated
a reduction in the limit of quantitation from 25nM (HD, human
plasma, in vitro) to 1.56nM. Sample and calibration stability
through the analytical sequence was established by the inclusion
of continuing calibration verification standards (< 5% error).
Short-term sample stability was verified by reinjection of a
calibration set after 18 days (R2 = 0.9997). Quantitative agreement
with the previous method was supported by the analysis of a 50nM
standard protein sample (HD, rat plasma) with both methodologies
(< 1% error).
Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
This
article is available in its entirety by fax for $40.00 each.
Visa, MasterCard and AMEX accepted.
To
order electronically click here
or call: 847-647-2900 ext. 1323
or fax request to: 847-647-1155.
To order multiple copies click here.
Please indicate JAT
volume and issue along with page numbers. |
|
Home | Subscribe
| Current Issue | Back Issues
| Search | Advertise | Other Publications
| |
