Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink discolouration and chemical–analytical interferences

Brunel, Christophe; Widmer, Christèle; Augsburger, Marc; Dussy, Franz; Fracasso, Tony

doi:10.1016/j.forsciint.2012.08.019

Cited by 10 publications

(8 citation statements)

References 14 publications

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“…Cyanide binds to cobalt to produce cyanocobalamin (vitamin B 12 ) [9–11], which resides in the plasma and is excreted in urine. The potential adverse effects of hydroxocobalamin are generally mild and include elevated blood pressure, decreased heart rate, rashes, and red coloring of the skin, tears, urine and sweat [12,13]. The recommended dose of hydroxocobalamin is 5 g (administered over 15 min).…”

Section: Introductionmentioning

confidence: 99%

Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry

Stutelberg

Vinnakota

Mitchell

et al. 2014

Journal of Chromatography B

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Accidental or intentional cyanide poisoning is a serious health risk. The current suite of FDA approved antidotes, including hydroxocobalamin, sodium nitrite, and sodium thiosulfate is effective, but each antidote has specific major limitations, such as large effective dosage or delayed onset of action. Therefore, next generation cyanide antidotes are being investigated to mitigate these limitations. One such antidote, 3-mercaptopyruvate (3-MP), detoxifies cyanide by acting as a sulfur donor to convert cyanide into thiocyanate, a relatively nontoxic cyanide metabolite. An analytical method capable of detecting 3-MP in biological fluids is essential for the development of 3-MP as a potential antidote. Therefore, a high performance liquid chromatography tandem mass spectrometry (HPLC-MS-MS) method was established to analyze 3-MP from rabbit plasma. Sample preparation consisted of spiking the plasma with an internal standard (13C3-3-MP), precipitation of plasma proteins, and reaction with monobromobimane to inhibit the characteristic dimerization of 3-MP. The method produced a limit of detection of 0.1 µM, a linear dynamic range of 0.5–100 µM, along with excellent linearity (R2 ≥ 0.999), accuracy (±9% of the nominal concentration) and precision (<7% relative standard deviation). The optimized HPLC-MS-MS method was capable of detecting 3-MP in rabbits that were administered sulfanegen, a prodrug of 3-MP, following cyanide exposure. Considering the excellent performance of this method, it will be utilized for further investigations of this promising cyanide antidote.

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Section: Introductionmentioning

confidence: 99%

Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry

Stutelberg

Vinnakota

Mitchell

et al. 2014

Journal of Chromatography B

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“…Pink colored skin and urine is a common and transient side-effect of hydroxycobalamin use [9][10][11]. In present case the skin coloration did not look like urticarial and might have resulted from other causes, like hematoma as some blood coagulation disorders were present on admission, or infection.…”

Section: Discussionmentioning

confidence: 61%

Pink skin, urine and effluent fluid after cyanide poisoning

Debord¹,

Bourdin²,

Stoian³

et al. 2013

J Med Disord

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We are reporting a fatal case of cyanide intoxication due to voluntary ingestion treated by hydroxycobalamin as antidote. Twelve hours after ICU admission abnormal pink colored skin and urines were observed. The effluent fluid removed during the continuous veno-venous hemofiltration treatment also exhibited pink colour. Even though pink coloured skin and urines is a well-known side-effect of the hydroxycobalamin use as an antidote for cyanide, such an abnormal colour of the effluent fluid has not been previously reported. Contrary to what has been described with the haemodialysis machines whose functioning may be impaired by hydroxycobalamin, the device used to perform continuous renal replacement therapy has worked properly in present case. Therefore, continuous renal replacement therapy should be the first choice method if needed in this setting.

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“…Cbl detoxifies cyanide through direct sequestration forming cyanocobalamin. The cyanocobalamin is then transported in blood by globulin, actively metabolized by the liver, processed by the kidney, and excreted through the urinary tract [39]. Therefore, sulfanegen, as with thiosulfate, may be utilized with Cbl to produce additive or synergistic effects.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Next Generation Cyanide Antidote Sulfanegen in Rabbits

Stutelberg

Monteil

Belani

et al. 2017

Int. J. Pharmacokinet.

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Aim: Sulfanegen has been shown to be an effective next generation cyanide antidote in multiple animal studies. Sulfanegen detoxifies cyanide by acting as a sulfur donor, converting cyanide to thiocyanate through the enzyme 3-mercaptopyruvate (3-MP) sulfurtransferase. The current study was performed to determine the PK behavior of sulfanegen in rabbits and compare it to current US FDA-approved cyanide therapeutics. Methods: Plasma sulfanegen concentrations, as 3-MP (i.e., sulfanegen is a prodrug that converts to the active sulfur donor, 3-MP, upon administration), were monitored using LC-MS/MS following intramuscular administration of sulfanegen in rabbits. Results: Concentrations of 3-MP rapidly increased following sulfanegen administration, indicating rapid absorption and distribution of 3-MP throughout the body. Elimination of 3-MP was also relatively rapid; the calculated half-life was approximately 114 min. A one-compartment model with first-order distribution and elimination was used to describe the PK behavior of 3-MP. Conclusion: Overall, the PK characteristics of sulfanegen were found to be well suited for the rapid treatment of cyanide poisoning.

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Antidote treatment for cyanide poisoning with hydroxocobalamin causes bright pink discolouration and chemical–analytical interferences

Cited by 10 publications

References 14 publications

Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry

Determination of 3-mercaptopyruvate in rabbit plasma by high performance liquid chromatography tandem mass spectrometry

Pink skin, urine and effluent fluid after cyanide poisoning

Pharmacokinetics of Next Generation Cyanide Antidote Sulfanegen in Rabbits

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