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Determination of Cyanide in Blood by Isotope Dilution Gas Chromatography-Mass Spectrometry



Karen E. Murphy, Michele M. Schantz, Therese A. Butler, Bruce A. Benner Jr, Laura J. Wood, Gregory C. Turk


A procedure based on isotope dilution gas chromatography/mass spectrometry (ID GC/MS) has been developed for the accurate and rapid determination of cyanide (CN) in whole blood. A known amount of isotopically labeled potassium cyanide (K13C15N) is added as the internal standard to 0.5 g whole blood in a headspace vial. Hydrogen cyanide is generated through the addition of phosphoric acid and after 5 min incubation; 0.5 mL of the headspace is injected into the GC/MS at 15 C oven temperature. The acid addition, incubation and injection steps have been fully automated. The peak areas of CN from the sample, 1H12C14N+ at m/z = 27 and the internal standard 1H13C15N+ at m/z = 29 are measured using single ion monitoring and the CN concentration in the sample is quantified by ID. The CN analysis takes less than 15 min. per sample. Accuracy of the procedure is demonstrated by measuring the CN content of unfrozen whole blood samples fortified with a known amount of CN. Reproducibility is demonstrated by periodic analyses over a fourteen month span. Results at the 0.6 g/g CN and 1.5 g/g CN levels show a reproducibility of 2.0 % (1s, n = 15) and 2.4 % (1s, n = 15), respectively. The average deviation from the known value for the two levels is less than 2 %. Results at the 0.06 g/g CN level were more variable, but still deviate on average less than 2.5 % from the known value. This method is suitable for forensic and clinical applications.
Clinical Chemistry


blood, cyanide, gas chromatography, head space, isotope dilution, mass spectrometry


Murphy, K. , Schantz, M. , Butler, T. , Benner, B. , Wood, L. and Turk, G. (2006), Determination of Cyanide in Blood by Isotope Dilution Gas Chromatography-Mass Spectrometry, Clinical Chemistry, [online], (Accessed May 28, 2024)


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Created March 31, 2006, Updated March 22, 2017