Determination of cyanide in blood by isotope-dilution gas chromatography-mass spectrometry.
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 degrees 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 microg/g were 8.3%, 5.4%, and 5.3%, respectively. The mean deviation from the known value for all concentrations was <4%.


CONCLUSIONS
The automated ID GC/MS method can accurately and rapidly quantify nanogram per gram to microgram per gram concentrations of CN in blood.
Murphy
Karen E
KE
National Institute of Standards and Technology, Gaithersburg, MD 20899, USA. karen.murphy@nist.gov
Schantz
Michele M
MM
Butler
Therese A
TA
Benner
Bruce A
BA
Wood
Laura J
LJ
Turk
Gregory C
GC
D001205:Ascorbic Acid; D002250:Carbon Radioisotopes; D003486:Cyanides / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006856:Hydrogen Cyanide / Q000097:blood; D007201:Indicator Dilution Techniques; D007202:Indicators and Reagents; D009587:Nitrogen Isotopes; D013696:Temperature; D035501:Uncertainty
D002250:Carbon Radioisotopes; D003486:Cyanides; D007202:Indicators and Reagents; D009587:Nitrogen Isotopes; D006856:Hydrogen Cyanide; D001205:Ascorbic Acid