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Clinical Chemistry 52: 458-467, 2006. First published January 26, 2006; 10.1373/clinchem.2005.061002
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(Clinical Chemistry. 2006;52:458-467.)
© 2006 American Association for Clinical Chemistry, Inc.


Drug Monitoring and Toxicology

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

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

1 National Institute of Standards and Technology, Gaithersburg, MD.

aAddress correspondence to this author at: National Institute of Standards and Technology, 100 Bureau Drive, Stop 8391, Gaithersburg, MD 20899. Fax 301-869-0413; e-mail karen.murphy{at}nist.gov.

Background: Cyanide (CN) is a lethal toxin. Quantification in blood is necessary to indicate exposure from many sources, including food, combustion byproducts, and terrorist activity. We describe an automated procedure based on isotope-dilution gas chromatography–mass spectrometry (ID GC/MS) for the accurate and rapid determination of CN in whole blood.

Methods: A known amount of isotopically labeled potassium cyanide (K13C15N) was added to 0.5 g of whole blood in a headspace vial. Hydrogen cyanide was generated through the addition of phosphoric acid, and after a 5-min incubation, 0.5 mL of the headspace was injected into the GC/MS at an oven temperature of –15 °C. The peak areas from the sample, 1H12C14N+, at m/z 27, and the internal standard, 1H13C15N+, at m/z 29, were measured, and the CN concentration was quantified by ID. The analysis time was 15 min for a single injection.

Results: We demonstrated method accuracy by measuring the CN content of unfrozen whole blood samples fortified with a known amount of CN. Intermediate precision was demonstrated by periodic analyses over a 14-month span. Relative expanded uncertainties based on a 95% level of confidence with a coverage factor of 2 at CN concentrations of 0.06, 0.6, and 1.5 µg/g were 8.3%, 5.4%, and 5.3%, respectively. The mean deviation from the known value for all concentrations was <4%.

Conclusion: The automated ID GC/MS method can accurately and rapidly quantify nanogram per gram to microgram per gram concentrations of CN in blood.







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