Metabolism of Cyanide by Glutathione To Produce the Novel Cyanide Metabolite 2-Aminothiazoline-4-oxoaminoethanoic Acid.

The direct analysis of cyanide (HCN or CN- inclusively symbolized as CN) to confirm exposure has major limitations due to cyanide's volatility, reactivity, and short half-life in biological fluids. These limitations have led to the exploration of cyanide detoxification products for indirect verification of cyanide exposure. Although cyanide interacts strongly with sulfur-containing molecules, to date, biomarkers resulting from the interaction of cyanide with glutathione (GSH; i.e., a biologically abundant sulfur-donating biomolecule) have yet to be discovered. In this study, we studied the interaction of CN and GSH to produce 2-aminothiazoline-4-oxoaminoethanioc acid (ATOEA). An LC-MS/MS method was developed and validated to analyze ATOEA from plasma, producing a linear range of 0.5-50 µM, a limit of detection of 200 nM, and excellent precision and accuracy. ATOEA concentrations were significantly elevated in the plasma of animals following cyanide exposure. Moreover, the production of ATOEA from cyanide exposure was confirmed by detection of both ATOEA and ATOEA-13C15N in rabbit plasma ( N = 11 animals) following administration of NaCN:K13C15N (1:1), with a similar amount of ATOEA and ATOEA-13C15N formed ( R2 = 0.9924, p < 0.05). The concentration of ATOEA increased with cyanide dose and then decreased rapidly when an antidote was administrated. This study definitively showed that ATOEA is produced from interaction of CN and GSH and can serve as a biomarker of cyanide exposure.

Cyanide poisoning is a possible cause of cardiac arrest among fire victims, and empiric antidote treatment may improve outcomes.

BACKGROUND: Carbon monoxide and cyanide poisoning are important causes of death due to fire. Carbon monoxide is more regularly assessed than cyanide at the site of burn or smoke inhalation treatment due to its ease in assessment and simplicity to treat. Although several forensic studies have demonstrated the significance of cyanide poisoning in fire victims using blood cyanide levels, the association between the cause of cardiac arrest and the concentration of cyanide among fire victims has not been sufficiently investigated. This study aimed to investigate the frequency of cyanide-induced cardiac arrest in fire victims and to assess the necessity of early empiric treatment for cyanide poisoning. METHODS: This study was a retrospective analysis of fire victims with cardiac arrest at the scene who were transported to a trauma and critical care center, Kyorin University Hospital, from January 2014 to June 2017. Patients whose concentration of cyanide was measured were included. RESULTS: Five patients were included in the study; all died despite cardiopulmonary resuscitation. Three of these victims were later found to have lethal cyanide levels (>3 µg/ml). Two of the patients had non-lethal carboxyhemoglobin levels under 50% and might have been saved if hydroxocobalamin had been administered during resuscitation. CONCLUSION: According to our results, cyanide-induced cardiac arrest may be more frequently present among fire victims than previously believed, and early empiric treatment with hydroxocobalamin may improve outcomes for these victims in cases where cardiac arrest is of short duration.

Concentrations of cyanide in blood samples of corpses after smoke inhalation of varying origin.

Cyanide (CN) blood concentration is hardly considered during routine when evaluating smoke gas intoxications and fire victims, although some inflammable materials release a considerable amount of hydrogen cyanide. CN can be significant for the capacity to act and can in the end even be the cause of death. Systematic data concerning the influence of different fire conditions, especially those of various inflammable materials, on the CN-blood concentration of deceased persons do not exist. This study measured the CN level in 92 blood samples of corpses. All persons concerned were found dead in connection with fires and/or smoke gases. At the same time, the carboxyhemoglobin (COHb) level was determined, and the corpses were examined to detect pharmaceutical substances, alcohol and drugs. Furthermore, we analysed autopsy findings and the investigation files to determine the inflammable materials and other circumstances of the fires. Due to the inflammable materials, the highest concentration of CN in the victims was found after enclosed-space fires (n = 45) and after motor-vehicle fires (n = 8). The CN levels in these two groups (n = 53) were in 47 % of the cases toxic and in 13 % of the cases lethal. In victims of charcoal grills (n = 17) and exhaust gases (n = 6), no or only traces of CN were found. Only one case of the self-immolations (n = 12) displayed a toxic CN level. The results show that CN can have considerable significance when evaluating action ability and cause of death with enclosed-space fires and with motor-vehicle fires.

Bioavailability of cyanide after consumption of a single meal of foods containing high levels of cyanogenic glycosides: a crossover study in humans.

The acute toxicity of cyanide is determined by its peak levels reached in the body. Compared to the ingestion of free cyanide, lower peak levels may be expected after consumption of foods containing cyanogenic glycosides with the same equivalent dose of cyanide. This is due to possible delayed and/or incomplete release of cyanide from the cyanogenic glycosides depending on many factors. Data on bioavailability of cyanide after consumption of foods containing high levels of cyanogenic glycosides as presented herein were necessary to allow a meaningful risk assessment for these foods. A crossover study was carried out in 12 healthy adults who consumed persipan paste (equivalent total cyanide: 68 mg/kg), linseed (220 mg/kg), bitter apricot kernels (about 3250 mg/kg), and fresh cassava roots (76-150 mg/kg), with each "meal" containing equivalents of 6.8 mg cyanide. Cyanide levels were determined in whole blood using a GC-MS method with K(13)C(15)N as internal standard. Mean levels of cyanide at the different time points were highest after consumption of cassava (15.4 µM, after 37.5 min) and bitter apricot kernels (14.3 µM, after 20 min), followed by linseed (5.7 µM, after 40 min) and 100 g persipan (1.3 µM, after 105 min). The double dose of 13.6 mg cyanide eaten with 200 g persipan paste resulted in a mean peak level of 2.9 µM (after 150 min). An acute reference dose of 0.075 mg/kg body weight was derived being valid for a single application/meal of cyanides or hydrocyanic acid as well as of unprocessed foods with cyanogenic glycosides also containing the accompanying intact ß-glucosidase. For some of these foods, this approach may be overly conservative due to delayed release of cyanide, as demonstrated for linseed. In case of missing or inactivated ß-glucosidase, the hazard potential is much lower.

A catalytic chemodosimetric approach for detection of nanomolar cyanide ions in water, blood serum and live cell imaging.

Naphthimidazolium based monocationic chemodosimeters CD-1 and CD-2 undergo cyanide mediated catalytic transformation in the presence of cyanide ions (0.01% to 1% of CD-1/CD-2 concentrations) with a turnover number from 70 to 360. These chemodosimeters can detect as low as 0.5 nM and 1 nM cyanide ions under nearly physiological conditions (HEPES buffer-DMSO (5%), pH 7.4). The structures of CD-1 and its cyanide induced hydrolyzed product 4 have been confirmed by single crystal X-ray crystallography. CD-1 can also be used for the determination of 2 nM cyanide in the presence of blood serum. CD-1 and CD-2 also find applications in live cell imaging of 10 nM cyanide ions in rat brain C6 glioma cells. To the best of our knowledge, this is the first report where high sensitivity towards cyanide ions has been achieved through catalytic hydrolysis of the fluorescent chemodosimeter.

The Metabolic Effects of Consumption of Yellow Cassava (Manihot esculenta Crantz) on Some Biochemical Parameters in Experimental Rats.

The metabolism of yellow cassava (variety TMS 01/1368) was investigated in male albino rats fed a diet containing yellow cassava for 7 to 28 days. There were significant increases (P < 0.05) in total and free cyanide and thiocyanate in the sera and urine samples of the experimental rats compared with the control, significant increases (P < 0.05) in serum glucose, alanine aminotransaminase, aspartate aminotransaminase, and alkaline phosphatase levels of the experimental rats compared with the control, significant decreases (P < 0.05) in serum albumin of the experimental rats compared with the control, but no significant differences (P > 0.05) in the serum total proteins of the experimental rats compared with the control. The experimental rats treated for 7, 14, 21, or 28 days exhibited body weight decreases of 5.11%, 11.10%, 19.16%, and 24.18%, respectively, whereas the control group showed 9.17% gain in body weight. Total and free cyanide concentrations were detected in the liver, kidney, and heart of most of the rats in both the experimental and control groups, except for free cyanide in the control group that was not detected. Metabolism of the yellow cassava variety in experimental rats was capable of exposing the animals to cyanide, underscoring the need for its proper processing before consumption by humans.

Development of a fluorescence-based sensor for rapid diagnosis of cyanide exposure.

Although commonly known as a highly toxic chemical, cyanide is also an essential reagent for many industrial processes in areas such as mining, electroplating, and synthetic fiber production. The "heavy" use of cyanide in these industries, along with its necessary transportation, increases the possibility of human exposure. Because the onset of cyanide toxicity is fast, a rapid, sensitive, and accurate method for the diagnosis of cyanide exposure is necessary. Therefore, a field sensor for the diagnosis of cyanide exposure was developed based on the reaction of naphthalene dialdehyde, taurine, and cyanide, yielding a fluorescent ß-isoindole. An integrated cyanide capture "apparatus", consisting of sample and cyanide capture chambers, allowed rapid separation of cyanide from blood samples. Rabbit whole blood was added to the sample chamber, acidified, and the HCN gas evolved was actively transferred through a stainless steel channel to the capture chamber containing a basic solution of naphthalene dialdehyde (NDA) and taurine. The overall analysis time (including the addition of the sample) was <3 min, the linear range was 3.13-200 µM, and the limit of detection was 0.78 µM. None of the potential interferents investigated (NaHS, NH4OH, NaSCN, and human serum albumin) produced a signal that could be interpreted as a false positive or a false negative for cyanide exposure. Most importantly, the sensor was 100% accurate in diagnosing cyanide poisoning for acutely exposed rabbits.

Simultaneous high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis of cyanide and thiocyanate from swine plasma.

An analytical procedure for the simultaneous determination of cyanide and thiocyanate in swine plasma was developed and validated. Cyanide and thiocyanate were simultaneously analyzed by high-performance liquid chromatography tandem mass spectrometry in negative ionization mode after rapid and simple sample preparation. Isotopically labeled internal standards, Na(13)C(15)N and NaS(13)C(15)N, were mixed with swine plasma (spiked and nonspiked), proteins were precipitated with acetone, the samples were centrifuged, and the supernatant was removed and dried. The dried samples were reconstituted in 10 mM ammonium formate. Cyanide was reacted with naphthalene-2,3-dicarboxaldehyde and taurine to form N-substituted 1-cyano[f]benzoisoindole, while thiocyanate was chemically modified with monobromobimane to form an SCN-bimane product. The method produced dynamic ranges of 0.1-50 and 0.2-50 µM for cyanide and thiocyanate, respectively, with limits of detection of 10 nM for cyanide and 50 nM for thiocyanate. For quality control standards, the precision, as measured by percent relative standard deviation, was below 8 %, and the accuracy was within ±10 % of the nominal concentration. Following validation, the analytical procedure successfully detected cyanide and thiocyanate simultaneously from the plasma of cyanide-exposed swine.

Can the cyanide metabolite, 2-aminothiazoline-4-carboxylic acid, be used for forensic verification of cyanide poisoning?

PURPOSE: Forensic verification of cyanide (CN) poisoning by direct CN analysis in postmortem blood is challenging due to instability of CN in biological samples. CN metabolites, thiocyanate (SCN-) and 2-aminothiazoline-4-carboxylic acid (ATCA), have been proposed as more stable biomarkers, yet it is unclear if either is appropriate for this purpose. In this study, we evaluated the behavior of CN biomarkers in postmortem swine and postmortem blood to determine which serves as the best biomarker of CN exposure. METHODS: CN, SCN-, and ATCA were measured in postmortem swine (N = 8) stored at 4 °C and postmortem blood stored at 25 °C (room temperature, RT) and 37 °C (typical human body temperature, HBT). RESULTS: Following CN poisoning, the concentration of each CN biomarker increased well above the baseline. In postmortem swine, CN concentrations declined rapidly (t1/2 = 34.3 h) versus SCN- (t1/2 = 359 h, 15 days) and ATCA (t1/2 = 544 h, 23 days). CN instability in postmortem blood increased at RT (t1/2 = 10.7 h) and HBT (t1/2 = 6.6 h). SCN- and ATCA were more stable than CN at all storage conditions. In postmortem swine, the t1/2s of SCN- and ATCA were 15 and 23 days, respectively. While both the t1/2s of SCN- and ATCA were relatively lengthy, endogenous levels of SCN- were much more variable than ATCA. CONCLUSION: While there are still questions to be answered, ATCA was the most adept forensic marker of CN poisoning (i.e., ATCA produced the longest half-life, the largest increase above baseline levels, and most stable background concentrations).

Pediatric cyanide poisoning by fire smoke inhalation: a European expert consensus. Toxicology Surveillance System of the Intoxications Working Group of the Spanish Society of Paediatric Emergencies.

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

Report on a study of fires with smoke gas development : determination of blood cyanide levels, clinical signs and laboratory values in victims.

BACKGROUND: This is a report on an international non-interventional study of patients exposed to fires with smoke development in closed rooms. The objective of the study was to document clinical symptoms, relevant laboratory values and blood cyanide concentrations from fire victims in order to confirm or rule out presumptive correlations between the individual parameters. MATERIALS AND METHODS: The study was conducted in five European countries with patients being included if they presented with the characteristic clinical signs, such as soot deposits and altered neurological status. Venous blood samples were taken from victims prior to administration of an antidote in all cases and determination of cyanide concentration was performed in a central laboratory using high performance liquid chromatography. RESULTS: Data from 102 patients (62 % male, average age 49 years) were included in the evaluation with no blood samples being available for analysis from 2 patients. In 25 patients the blood cyanide concentration was below the limit of detection of 1.2 µmol/l. Cyanide levels between 1.2 and 10 µmol/l were measured in 54 patients, 7 patients had values between 10 and 20 µmol/l, 4 patients between 20 and 40 µmol/l while levels above 40 µmol/l were determined in 10 patients. The results of the study could not demonstrate that the cyanide level was influenced either by the interval between smoke exposure and blood sampling or the duration presence at the fire scene. The following clinical signs or laboratory values were recorded as relevant for increased and possibly toxic cyanide levels: respiratory arrest, dyspnea, resuscitation requirement, tracheal intubation, respiratory support measures, low Glasgow coma scale (GCS) score and respiratory frequency. A correlation between cyanide concentration and the total amount of soot deposits on the face and neck, in the oral cavity and in expectoration was confirmed. A correlation between cyanide and carboxyhemoglobin (COHb) levels in the blood of fire victims was also confirmed. CONCLUSIONS: As long as it is not possible to immediately determine the blood cyanide concentration in patients exposed to fire with smoke development, a decreased GCS score, soot deposits particularly in expectoration, dyspnea and convulsions are to be regarded as risk markers for intoxication. In their presence immediate administration of hydroxocobalamin as an antidote is recommended.

Comparison of cyanide exposure markers in the biofluids of smokers and non-smokers.

Cyanide is highly toxic and is present in many foods, combustion products (e.g. cigarette smoke), industrial processes, and has been used as a terrorist weapon. In this study, cyanide and its major metabolites, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid (ATCA), were analyzed from various human biofluids of smokers (low-level chronic cyanide exposure group) and non-smokers to gain insight into the relationship of these biomarkers to cyanide exposure. The concentrations of each biomarker tested were elevated for smokers in each biofluid. Significant differences (p < 0.05) were found for thiocyanate in plasma and urine, and ATCA showed significant differences in plasma and saliva. Additionally, biomarker concentration ratios, correlations between markers of cyanide exposure, and other statistical methods were performed to better understand the relationship between cyanide and its metabolites. Of the markers studied, the results indicate plasma ATCA, in particular, showed excellent promise as a biomarker for chronic low-level cyanide exposure.

Rapid and highly selective dipchecking for cyanide ions in aqueous media.

This article reports a simple dipping method for the detection of cyanide ions in water and biological samples, such as blood, using chitosan-gold nanoparticle (CH-Au NP) composite films prepared using CH-Au NP colloids. Here, gold nanoparticles were generated by heating (to ~80 °C) a solution of chitosan and gold chloride, where chitosan plays the dual role of reducing and stabilizing agent. The well-known chemistry of leaching of gold by cyanide is exploited here to detect cyanide ions. The CH-Au films showed the localized surface plasmon resonance (LSPR) absorption, similar to the CH-Au colloidal solution, at 534 nm. Gold nanoparticles (Au NPs) in the films are found to be dissolved quantitatively, causing a proportional decrease in intensity of the LSPR peak. Color change was observable by the naked eye above a concentration of 2 mg L(-1) of CN(-) in solution. We found a good correlation between the reduction in intensity of the absorption peak at 534 nm and concentrations of CN(-) ions as low as 0.06 mg L(-1). Most of the previously reported methods for cyanide detection involve tedious chemistry, demand the use of sophisticated instruments and still are not suitable for on-site cyanide monitoring. Our reported approach is rapid, eco-friendly, low cost, easy to use, and highly selective for cyanide detection in aqueous solution. We feel that this simple, low cost, novel and portable method is suitable particularly for third world countries, where more sophisticated aids are not so common.

Hydroxocobalamin and epinephrine both improve survival in a swine model of cyanide-induced cardiac arrest.

STUDY OBJECTIVE: To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. METHODS: Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. RESULTS: Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48%) hydroxocobalamin animals and in 11 of 11 (100%; 95% CI 70% to 100%) of the epinephrine animals (P<.001). At 60 minutes, serum lactate was significantly lower in the hydroxocobalamin group compared with the epinephrine group (4.9 [SD 2.2] versus 12.3 [SD 2.2] mmol/L), and the pH was significantly higher (7.34 [SD 0.03] versus 7.15 [SD 0.07]). Serial blood cyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. CONCLUSION: Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased blood lactate and cyanide levels, and decreased the use of rescue epinephrine therapy compared with that in the epinephrine group.

Simultaneous determination of cyanide and thiocyanate in plasma by chemical ionization gas chromatography mass-spectrometry (CI-GC-MS).

An analytical method utilizing chemical ionization gas chromatography-mass spectrometry was developed for the simultaneous determination of cyanide and thiocyanate in plasma. Sample preparation for this analysis required essentially one-step by combining the reaction of cyanide and thiocyanate with pentafluorobenzyl bromide and simultaneous extraction of the product into ethyl acetate facilitated by a phase-transfer catalyst, tetrabutylammonium sulfate. The limits of detection for cyanide and thiocyanate were 1 µM and 50 nM, respectively. The linear dynamic range was from 10 µM to 20 mM for cyanide and from 500 nM to 200 µM for thiocyanate with correlation coefficients higher than 0.999 for both cyanide and thiocyanate. The precision, as measured by %RSD, was below 9 %, and the accuracy was within 15 % of the nominal concentration for all quality control standards analyzed. The gross recoveries of cyanide and thiocyanate from plasma were over 90 %. Using this method, the toxicokinetic behavior of cyanide and thiocyanate in swine plasma was assessed following cyanide exposure.

Cyanide toxicity in juvenile pigs and its reversal by a new prodrug, sulfanegen sodium.

BACKGROUND: Cyanide (CN) toxicity is a serious clinical problem and can occur with sodium nitroprusside (SNP) administration, accidental smoke inhalation, industrial mishaps, and bio-terrorism. In this study, we induced severe CN toxicity independently with SNP or sodium cyanide (NaCN) in a juvenile pig model to demonstrate reversal of severe CN toxicity with a new antidote, sulfanegen sodium, a prodrug of 3-mercaptopyruvate. METHODS: SNP study: A pilot study in 11 anesthetized, mechanically ventilated juvenile pigs allowed us to determine the dose of SNP to induce CN toxicity. Blood CN, serum lactates, and blood gases were monitored. CN toxicity was defined as the occurrence of severe lactic acidosis accompanied by significant elevation in blood CN levels. Based on this pilot study, 8 anesthetized pigs received a high-dose i.v. infusion of SNP (100 mg/h) for 2 hours to induce CN toxicity. They were then randomized to receive either sulfanegen sodium or placebo. Four pigs received 3 doses of sulfanegen sodium (2.5 g i.v.) every hour after induction of severe CN toxicity, and 4 pigs received placebo. NaCN study: A pilot study was conducted in 4 spontaneously ventilating pigs sedated with propofol plus ketamine to demonstrate hemodynamic and metabolic stability for several hours. After this, 6 pigs were similarly sedated and given NaCN in bolus aliquots to produce CN toxicity ultimately resulting in death. Hemodynamics and metabolic variables were followed to define peak CN toxicity. In another group of 6 pigs, severe CN toxicity was induced by this method, and at peak toxicity, the animals were given sulfanegen sodium (2.5 g i.v.) followed by a repeat dose 60 minutes later in surviving animals. RESULTS: SNP study: The pilot study demonstrated the occurrence of a significant increase in blood CN levels (P < 0.05) accompanied by severe lactic acidemia (P < 0.05) in all pigs receiving a high dose of SNP. Administration of the sulfanegen antidote resulted in progressive significant reduction in blood lactate and CN levels with 100% survival (P < 0.05), whereas the placebo-treated pigs deteriorated and did not survive (P < 0.05). NaCN study: NaCN injection resulted in CN toxicity accompanied by severe lactic acidosis and mortality in all the pigs. Sulfanegen sodium reversed this toxicity and prevented mortality in all the pigs treated with this antidote. CONCLUSIONS: CN toxicity can be successfully induced in a juvenile pig model with SNP or NaCN. The prodrug, sulfanegen sodium, is effective in reversing CN toxicity induced by SNP or NaCN.

Swedish forensic data 1992-2009 suggest hydrogen cyanide as an important cause of death in fire victims.

Between 60 and 80% of all deaths related to fire are attributed to toxic fumes. Carbon monoxide (CO) is commonly thought to be the major cause. However, hydrogen cyanide (HCN) is also formed. Still, the exact contribution of HCN to fire-related fatalities is unknown. The aim of the study was to investigate the impact of HCN in relation to CO as a cause of death in fire victims. Data on carboxyhemoglobin (COHb) and blood cyanide from deceased fire victims in the period 1992-2009 were collected from two Swedish nationwide forensic databases (ToxBase and RättsBase). The databases contain data on COHb and/or cyanide from 2303 fire victims, whereof 816 on both COHb and cyanide. Nonparametric statistical tests were used. Seventeen percent of the victims had lethal or life-threatening blood cyanide levels (>1 µg/g) and 32% had lethal COHb levels (>50% COHb). Over 31% had cyanide levels above 0.5 µg/g, an indication of significant HCN exposure. The percentages may be underestimates, as cyanide is quickly eliminated in blood also after death. Our results support the notion that HCN contributes more to the cause of death among fire victims than previously thought.

[Measurement of acetonitrile in blood and urine by head-space gas chromatography].

OBJECTIVE: To establish the method for measurement of acetonitrile in blood and urine by head-space gas chromatography. METHODS: DB-ALC1 (30 m x 320 microm x 1.8 microm) and DB-ALC2 (30 m x 320 microm x 1.2 microm) capillary column were used to measure the acetonitrile in blood and urine with the isopropanol as internal standard reference. RESULTS: The limits of detection of acetonitrile in both blood and urine were 0.5 microg/mL, with a linear range of 5-1000 microg/mL (r = 0.999).The accuracy of this method was 93.2%-98.0%. The RSD for the intra-day and inter-day were less than 3.7%. CONCLUSION: The method is capable for measurement analysis of acetonitrile in blood and urine.

A novel method for cyanide quantification in human whole blood using ion chromatography with amperometric detection and its application to cyanide intoxication cases.

Cyanide is a highly toxic agent that has been frequently used for suicide in South Korea. It is also used in various industrial fields, such as metal plating, in which many accidental cyanide intoxications have occurred. To overcome the disadvantages of conventional cyanide analysis methods, a simple and fast method for the analysis of cyanide in whole blood using ion chromatography (IC) with amperometric detection was developed in this study. Whole blood samples were deproteinized, diluted, and analyzed using an IC-amperometric detection system. The limits of detection and quantitation were 0.1 and 0.2 mg/L, respectively. The method showed good linearity in the range of 0.2 to 50 mg/L with R2  > 0.99. The intra- and inter-assay precision and accuracy values were <10%. The established method was successfully applied to analyze whole blood samples from three cyanide intoxication cases.

Rapid point of care analyzer for the measurement of cyanide in blood.

A simple, sensitive optical analyzer for the rapid determination of cyanide in blood in point of care applications is described. HCN is liberated by the addition of 20% H(3)PO(4) and is absorbed by a paper filter impregnated with borate-buffered (pH 9.0) hydroxoaquocobinamide (hereinafter called cobinamide). Cobinamide on the filter changes color from orange (λ(max) = 510 nm) to violet (λ(max) = 583 nm) upon reaction with cyanide. This color change is monitored in the transmission mode by a light emitting diode (LED) with a 583 nm emission maximum and a photodiode detector. The observed rate of color change increases 10 times when the cobinamide solution for filter impregnation is prepared in borate-buffer rather than in water. The use of a second LED emitting at 653 nm and alternate pulsing of the LEDs improves the limit of detection by 4 times to ~0.5 µM for a 1 mL blood sample. Blood cyanide levels of imminent concern (≥10 µM) can be accurately measured in ~2 min. The response is proportional to the mass of cyanide in the sample: smaller sample volumes can be successfully used with proportionate change in the concentration LODs. Bubbling air through the blood-acid mixture was found effective for mixing of the acid with the sample and the liberation of HCN. A small amount of ethanol added to the top of the blood was found to be the most effective means to prevent frothing during aeration. The relative standard deviation (RSD) for repetitive determination of blood samples containing 9 µM CN was 1.09% (n = 5). The technique was compared blind with a standard microdiffusion-spectrophotometric method used for the determination of cyanide in rabbit blood. The results showed good correlation (slope 1.05, r(2) 0.9257); independent calibration standards were used.