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

• Published in: Journal of analytical toxicology Vol. 28; no. 5; pp. 384 - 389
• Main Authors: Byers, C.E., Holloway, E.R., Korte, W.D., Smith, J.R., Clarkson, E.D., Platoff, G.E., Capacio, B.R.
• Format: Journal Article
• Language: English
• Published: Niles, IL Oxford University Press 01-07-2004; Preston
• Subjects: Analysis; Animals; Biological and medical sciences; Chelating Agents - administration & dosage; Chelating Agents - analysis; Chelating Agents - pharmacokinetics; Chemical and industrial products toxicology. Toxic occupational diseases; Dimercaprol - administration & dosage; Dimercaprol - blood; Dimercaprol - pharmacokinetics; Disease Models, Animal; Gas Chromatography-Mass Spectrometry - methods; Gas, fumes; General pharmacology; Guinea Pigs; Injections, Intramuscular; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; Swine; Toxicology; Solid phase extraction; Biological fluid; Chemical analysis; Dimercaprol; 2-chlorovinyl dichloroarsine; Derivatization; Blood; Chemical enrichment; Blood plasma; Chemical warfare agent; Guinea pig; Sample preparation; Acylation; Quantitative analysis; Coupled method; Rodentia; Sulfur mustard; Gas chromatography; Vertebrata; Mammalia; Mercaptoalcohol; Animal; Chelating agent; Antidote; Pharmacokinetics; Mass spectrometry; Arsenic Organic compounds
• ISSN: 0146-4760; 1945-2403
• DOI: 10.1093/jat/28.5.384

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.