Gas chromatographic-mass spectrometric determination of british anti-lewisite in plasma.
British anti-Lewisite (BAL) (2,3-dimercapto-1-propanol) is a potential therapeutic compound when used against the effects of cutaneous sulfur mustard, and a method for its determination in plasma has been developed. BAL and the internal standard (IS) ethane dithiol were isolated from plasma samples through solid-phase extraction and then reacted with 1-pentafluoropropionylimidazole, forming stable pentafluoropropionyl derivates that are sensitive to gas chromatographic-mass spectrometric analysis. Examination of concentration versus peak-area ratios of the BAL and IS derivatives demonstrated the method to be linear over a concentration range of 0.48 to 124 ng/mL in plasma when fit to a weighted (1/y2) least-squares regression. Correlation coefficients were 0.9943 to 0.9995 for six runs, and coefficients of variation (CV) were 2.5 to 8.7% over the eight concentrations tested. The intra- and interday accuracy and precision of this method was measured by examining six groups of eight unknown test samples (n = 6). Intraday accuracy, as expressed by percent error, was found to range from -15.4 to 0.21%, whereas the precision, expressed as %CV, was less than 9.8% over all sample concentrations. Interday test unknown sample results were similar in that the accuracy was shown to be -7.1 to 0.4%, and precision was 4.7 to 9.5%. BAL levels in frozen plasma (-70 degrees C) remained constant for more than 14 days with a CV of less than 10% for the eight concentrations tested. The data indicate that the method will provide accurate and precise determination of BAL at concentrations down to approximately 1 ng/mL in plasma. This procedure has been applied to determine preliminary time-concentration profile studies of BAL in the hairless guinea pig.
Byers
C E
CE
U.S. Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, Maryland 21010-5400, USA.
Holloway
E R
ER
Korte
W D
WD
Smith
J R
JR
Clarkson
E D
ED
Platoff
G E
GE
Capacio
B R
BR
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D004112:Dimercaprol / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006168:Guinea Pigs; D007273:Injections, Intramuscular; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013552:Swine
D002614:Chelating Agents; D004112:Dimercaprol