Validation and Application of a GC-MS Method for Determining Soman Concentration in Rat Plasma Following Low-Level Vapor Exposure

A method for determining the chemical warfare agent soman (GD) in rat plasma has been validated and applied to low-level inhalation exposure studies currently being conducted. This method utilizes a fluoride ion-based regeneration assay with isotope dilution followed by large volume injection gas ch...

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Bibliographic Details
Published in:Journal of analytical toxicology 2008, Vol.32 (1), p.92-98
Main Authors: Renner, Julie A., Dabisch, Paul A., Evans, Ronald A., McGuire, Jeffrey M., Totura, Allison L., Jakubowski, Edward M., Thomson, Sandra A.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Animals
Calibration
Chemical Warfare Agents - analysis
Chemical Warfare Agents - pharmacokinetics
Cholinesterase Inhibitors - administration & dosage
Cholinesterase Inhibitors - blood
Cholinesterase Inhibitors - pharmacokinetics
Environmental Exposure - analysis
Environmental Monitoring - methods
Fluorides - chemistry
Gas Chromatography-Mass Spectrometry - methods
Male
Potassium Compounds - chemistry
Rats
Rats, Sprague-Dawley
Reproducibility of Results
Solid Phase Extraction
Soman - administration & dosage
Soman - blood
Soman - pharmacokinetics
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Summary:A method for determining the chemical warfare agent soman (GD) in rat plasma has been validated and applied to low-level inhalation exposure studies currently being conducted. This method utilizes a fluoride ion-based regeneration assay with isotope dilution followed by large volume injection gas chromatography with ammonia chemical ionization mass spectrometric detection. Following sample preparation by solid phase extraction, chromatographic separation was achieved using a 14% cyanopropylphenyl/86% dimethyl polysiloxane capillary column with a total run time of 18.16 min. Soman and the deuterated isotope (2H4-soman) internal standard were detected using the selected ion monitoring mode and quantitated using the ammonia adduction ratio of m/z ions 200/204. A reproducible linear relationship was obtained for the quantitative concentration range of 10 pg on-column to 1000 pg on-column (r2 = 0.9995) for standards in ethyl acetate with a detection limit of 5.65 pg on-column, and an average recovery of 93% in plasma. This sensitive method was successfully applied to the analysis of soman in rat plasma immediately post-exposure, resulting in the construction of dose-response plots.
ISSN:0146-4760
1945-2403
DOI:10.1093/jat/32.1.92