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 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 ((2)H(4)-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 (r(2) = 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.
Renner
Julie A
JA
SAIC, Gunpowder Branch, Aberdeen Proving Ground, Maryland 21010-0068, USA. julie.a.renner@us.army.mil
Dabisch
Paul A
PA
Evans
Ronald A
RA
McGuire
Jeffrey M
JM
Totura
Allison L
AL
Jakubowski
Edward M
EM
Thomson
Sandra A
SA
D000280:Administration, Inhalation; D000818:Animals; D002138:Calibration; D002619:Chemical Warfare Agents / Q000032:analysis / Q000493:pharmacokinetics; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring / Q000379:methods*; D005459:Fluorides / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D008297:Male; D017680:Potassium Compounds / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D012999:Soman / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D017680:Potassium Compounds; C033320:potassium fluoride; D012999:Soman; D005459:Fluorides