Application of 2-Aminothiazoline-4-carboxylic Acid as a Forensic Marker of Cyanide Exposure

Abstract

Cyanides are infamous for their highly poisonous properties. Accidental cyanide poisoning occurs frequently, but occasionally, intentional poisonings also occur. Inhalation of fumes generated by fire may also cause cyanide poisoning. There are many limitations in direct analysis of cyanide. 2-Aminothiazoline-4-carboxylic acid (ATCA), a cyanide metabolite, seems to be the only surrogate that is being used in the detection of cyanide because of its stability and its cyanide-dependent quality in a biological matrix. Unfortunately, toxicokinetic studies on diverse animal models suggest significant interspecies differences; therefore, the attempt to extrapolate animal models to human models may be unsuccessful. The aim of the present study was to evaluate the use of ATCA as a forensic marker of cyanide exposure. For this purpose, post-mortem materials (blood and organs) from fire victims (n = 32) and cyanide-poisoned persons (n = 3) were collected. The distribution of ATCA in organs and its thermal stability were evaluated. The variability of cyanides in a putrid sample and in the context of their long-term and higher temperature stability was established. The presence of ATCA was detected by using an LC-MS/MS method and that of cyanide was detected spectrofluorimetrically. This is the first report on the endogenous ATCA concentrations and the determination of ATCA distribution in tissues of fire victims and cyanide-poisoned persons. It was found that blood and heart had the highest ATCA concentrations. ATCA was observed to be thermally stable even at 90 °C. Even though the cyanide concentration was not elevated in putrid samples, it was unstable during long-term storage and at higher temperature, as expected. The relationship between ATCA and cyanides was also observed. Higher ATCA concentrations were related to increased levels of cyanide in blood and organs (less prominent). ATCA seems to be a reliable forensic marker of exposure to lethal doses of cyanide.

RECiQ: A Rapid and Easy Method for Determining Cyanide Intoxication by Cyanide and 2-Aminothiazoline-4-carboxylic Acid Quantification in the Human Blood Using Probe Electrospray Ionization Tandem Mass Spectrometry

“…As presented in Table 3 , the ATCA blood concentrations of victims of fire incidents ranged from 100 to 191 ng/mL in previous reports. 16 However, our results revealed higher ATCA blood concentration levels. Although the reason for this was not discussed in this study, there may have been a difference in the periods between CN exposure and death or a racial difference in the metabolism of CN to ATCA.…”

“…The endogenous and exogenous levels of CN and ATCA in the human blood are presented in Table 3 . 10 , 15 , 16 , 28 , 34 − 36 It became apparent that the present methods can be applied to the concentration ranges of fire incidents and CN poisoning and are satisfactory for forensic purposes. The raw data of the calibrants and QC samples are presented in Tables S2 and S3 .…”

“…Ruzycka et al have reported that ATCA functions as an indicator of CN intoxication, though perhaps not at sublethal levels. 16 However, an animal study by Yu et al has demonstrated that plasma ATCA concentration levels increased significantly with sublethal CN dose levels. 9 In addition, there have been several reports on ATCA in cases of CN exposure in the United States and Europe, but none from Asia.…”

“… 7 − 18 It is produced by the reaction of cystine with CN; approximately 20% of the injected CN is metabolized to ATCA 8 , 14 and does not metabolize further. 14 Additionally, ATCA is stable in the blood, 16 making it a suitable analytical target to indicate CN exposure. Ruzycka et al have reported that ATCA functions as an indicator of CN intoxication, though perhaps not at sublethal levels.…”

Development of magnetic carbon nanotubes for dispersive micro solid phase extraction of the cyanide metabolite, 2-aminothiazoline-4-carboxylic acid, in biological samples

“…However, the high volatility and short half-life (t 1/2 = 0.34 -1.28 hours) of cyanide narrow the detection window for successful analysis [19]. Previous studies also revealed that cyanide concentration fluctuates over time and at various temperatures upon storage [20,21]. These create a challenge for the confirmation of exposure due to the difficulty in interpreting the cyanide concentration.…”