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

Abstract

In this study, we developed a rapid and easy method to determine cyanide (CN) intoxication by quantification of CN and 2-aminothiazoline-4-carboxylic acid (ATCA), which is a new and reliable indicator of CN exposure, in the human blood using probe electrospray ionization tandem mass spectrometry (PESI/MS/MS) named RECiQ. For CN, we applied the previously reported one-pot derivatization method using 2,3-naphthalenedialdehyde and taurine, which can directly derivatize CN in the blood. The analytical conditions of the CN derivatization were optimized as a 10 min reaction time at room temperature. In contrast, ATCA could be directly detected in the blood by PESI/MS/MS. We developed quantitative methods for the derivatized CN and ATCA using an internal standard method and validated them using quality control samples, demonstrating that the linearities of each calibration curve were greater than 0.995, and intra- and interday precisions and accuracies were 5.1–15 and 1.1–14%, respectively. Moreover, the lower limit of detections for CN and ATCA were 42 and 43 ng/mL, respectively. Finally, we applied RECiQ to three postmortem blood specimens obtained from victims of fire incidents, which resulted in the successful quantification of CN and ATCA in all samples. As PESI/MS/MS can be completed within 0.5 min, and the sample volume requirement of RECiQ is only 2 μL of blood, these methods are useful not only for the rapid determination of CN exposure but also for the estimation of the CN intoxication levels during an autopsy.

Performance comparison between solid phase extraction and magnetic carbon nanotubes facilitated dispersive-micro solid phase extractions (Mag-CNTs/d-µSPE) of a cyanide metabolite in biological samples using GC–MS

“…The majority of the post-mortem ATCA analyses focused on measuring endogenous ATCA levels in autopsy blood samples collected from non-cyanide-related cases and fire victims. These data confirmed an elevated ATCA concentration could be detected from the autopsy blood due to the potential exposure of cyanide produced in fire scenes (Rużycka et al 2017;Hisatsune et al 2020;Luliński et al 2015). The promising results of the Mag-CNTs/d-µSPE/GC-MS assay in synthetic urine and bovine blood samples could encourage inter-agency research to accelerate the groundwork for the use of ATCA as forensic evidence in death investigation related to cyanide exposure.…”

“…Satisfactory recoveries and sensitivities were obtained from the commercially available d-µSPE sorbent and in some MIPs. And with the rapid advancement in ambient ionization technique, ATCA was detected almost in real-time from sample collection to analysis with minimal sample preparation and consumption (Hisatsune et al 2020). However, the limited access to tandem mass spectrometry instrumentation due to the high cost might restrict the Li et al J Anal Sci Technol (2021) 12:42 applications of these methods to most regional forensic laboratories.…”

Applications of ambient ionization mass spectrometry in 2020: An annual review

“…Hisastune et al applied PESI‐MS to the analysis of human whole blood for the purpose of detecting cyanide and 2‐aminothiazoline‐4‐carboxylic acid, compounds indicative of cyanide poisoning. The technique achieved detection limits of 42 and 43 ng/mL, respectively 70 . DART‐MS has been applied to the detection of exogenous materials in body fluids.…”

“…The technique achieved detection limits of 42 and 43 ng/mL, respectively. 70 DART‐MS has been applied to the detection of exogenous materials in body fluids. Liang et al used transmission mode‐DART‐MS, in which microliter samples of biofluid are first deposited onto a wire mesh substrate prior to exposure to the DART ion source, enabling reproducible sample positioning.…”

Easily Operable Quantification Method of 21 Plant-Derived Alkaloids in Human Serum by Automatic Sample Preparation and Liquid Chromatography–Tandem Mass Spectrometry

“…Moreover, new mass spectrometric techniques, called ambient ionization mass spectrometry (AIMS), require little or no sample pretreatment [ 7 ]. AIMS, such as desorption electrospray ionization (DESI) [ 8 , 9 ] and probe electrospray ionization (PESI) [ 10 – 13 ], are defined as ionization techniques for analysis under open-air conditions, allowing high-throughput analysis of toxins to be performed. However, AIMS need special ionization sources and deep knowledge for mass spectrometry; thus, they are not conventional techniques.…”