Document Type
Article
Publication Date
1-2016
Abstract
The current suite of Food and Drug Administration (FDA) approved antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide antidotes. Therefore, a liquid chromatography–tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard (13C3-3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN)2). The limits of detection for 3-MP and Cbi were 0.5 μM and 0.2 μM, respectively. The linear ranges were 2–500 μM for 3-MP and 0.5–50 μM for Cbi. The accuracy and precision for 3-MP were 100 ± 9% and <8.3% relative standard deviation (RSD), respectively. For Cbi(CN)2, the accuracy was 100 ± 13% and the precision was <9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these antidotes for treatment of cyanide poisoning.
Publication Title
Journal of Chromatography B
Volume
1008
First Page
181
Last Page
188
Format
applicationen/pdf
Language
en
DOI of Published Version
10.1016/j.jchromb.2015.11.027
Publisher
Elsevier
Rights
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S.
Recommended Citation
Stutelberg, Michael W.; Dzisam, Joseph K.; Monteil, ALexandre R.; Petrikovics, Ilona; Boss, Gerry R.; Patterson, Steven E.; Rockwood, Gary A.; and Logue, Brian A., "Simultaneous Determination of 3-mercaptopyruvate and Cobinamide in Plasma by Liquid Chromatography–tandem Mass Spectrometry" (2016). Chemistry and Biochemistry Faculty Publications. 74.
https://openprairie.sdstate.edu/chem_pubs/74