Journal Article

Gas Chromatographic-Mass Spectrometric Determination of British Anti-Lewisite in Plasma

C.E. Byers, E.R. Holloway, W.D. Korte, J.R. Smith, E.D. Clarkson, G.E. Platoff and B.R. Capacio

in Journal of Analytical Toxicology

Volume 28, issue 5, pages 384-389
Published in print July 2004 | ISSN: 0146-4760
Published online July 2004 | e-ISSN: 1945-2403 | DOI: https://dx.doi.org/10.1093/jat/28.5.384
Gas Chromatographic-Mass Spectrometric Determination of British Anti-Lewisite in Plasma

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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/γ2) 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°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.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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