Determination of cyanide in blood by electrospray ionization tandem mass spectrometry after direct injection of dicyanogold

Abstract

An electrospray ionization tandem mass spectrometric (ESI-MS-MS) method has been developed for the determination of cyanide (CN(-)) in blood. Five microliters of blood was hemolyzed with 50 μL of water, then 5 μL of 1 M tetramethylammonium hydroxide solution was added to raise the pH of the hemolysate and to liberate CN(-) from methemoglobin. CN(-) was then reacted with NaAuCl(4) to produce dicyanogold, Au(CN)(2)(-), that was extracted with 75 μL of methyl isobutyl ketone. Ten microliters of the extract was injected directly into an ESI-MS-MS instrument and quantification of CN(-) was performed by selected reaction monitoring of the product ion CN(-) at m/z 26, derived from the precursor ion Au(CN)(2)(-) at m/z 249. CN(-) could be measured in the quantification range of 2.60 to 260 μg/L with the limit of detection at 0.56 μg/L in blood. This method was applied to the analysis of clinical samples and the concentrations of CN(-) in the blood were as follows: 7.13 ± 2.41 μg/L for six healthy non-smokers, 3.08 ± 1.12 μg/L for six CO gas victims, 730 ± 867 μg for 21 house fire victims, and 3,030 ± 97 μg/L for a victim who ingested NaCN. The increase of CN(-) in the blood of a victim who ingested NaN(3) was confirmed using MS-MS for the first time, and the concentrations of CN(-) in the blood, gastric content and urine were 78.5 ± 5.5, 11.8 ± 0.5, and 11.4 ± 0.8 μg/L, respectively.

A rapid and decisive determination of thiocyanate in blood by electrospray ionization tandem mass spectrometry

“…A possible reason for this is that a large amount of endogenous SCN -may, to some extent, undergo the same chemical reaction as that induced by a small amount of CN -. Although the chelating reaction of SCN -with Au ion used in this study is the same as that for CN - [15,16], their identification and quantification can be achieved independently on MS-MS because their mass to charge ratios (i.e., 58 and 26) are different. That is, the concentration of SCNin 5 ll of blood could be determined within 15 min using the present method, while the concentration of CN -in 5 ll of blood could be determined within 10 min using the previous method [16].…”

“…Although the chelating reaction of SCN -with Au ion used in this study is the same as that for CN - [15,16], their identification and quantification can be achieved independently on MS-MS because their mass to charge ratios (i.e., 58 and 26) are different. That is, the concentration of SCNin 5 ll of blood could be determined within 15 min using the present method, while the concentration of CN -in 5 ll of blood could be determined within 10 min using the previous method [16]. The method presented here is therefore suitable for rapid and decisive identification and quantification of SCN -in forensic toxicology screening.…”

“…The recovery of SCN -at 1 lM in 100-fold diluted blood was less than 5%. Although CN -and N 3 -are mainly distributed in erythrocytes and tightly bound to methemoglobin [4,16], SCN -is mainly distributed in plasma and has a weak electrostatic association with albumin [17]. The low recovery of SCN -from blood may be due to the occlusion of SCN -and Au ion by proteins coagulated with octanol.…”

Ultra-sensitive determination of cyanide in surface water by gas chromatography–tandem mass spectrometry after derivatization with 2-(dimethylamino)ethanethiol

“…High performance liquid chromatography (HPLC) methods [29][30][31][32][33][34][35], liquid chromatography-tandem mass spectrometry (LC-MS/MS) [36][37][38][39][40][41], and direct injection MS/MS [42,43] have previously been reported in the analysis of cyanide. In these methods, cyanide was derivatized with reagents including 2,3-naphthalenedialdehyde [29][30][31][32][33][34][35][36][37][38]41],o-phthalaldehyde [32,33], quinoline and benzoyl chloride [32], and metal-ligand reagents [35,39,40].…”

Derivatization Method of Free Cyanide Including Cyanogen Chloride for the Sensitive Analysis of Cyanide in Chlorinated Drinking Water by Liquid Chromatography-Tandem Mass Spectrometry

“…22 30 and metal−ligand reagents. 33,37,38 Many LC-MS/ MS methods for determining cyanide in biological samples that do not employ derivatization have been developed. 37,38 However, these methods suffer from low sensitivity and interference and require additional cleanup steps.…”