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Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate

Novel cyanide countermeasures are needed for cases of a mass-exposure cyanide emergency. A lead candidate compound is dimethyl trisulfide (DMTS), which acts as a sulfur donor for rhodanese, thereby assisting the conversion of cyanide into thiocyanate. DMTS is a safe compound for consumption and, in...

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Autores principales: Bartling, Craig M., Andre, Jon C., Howland, Carrie A., Hester, Mark E., Cafmeyer, Jeffrey T., Kerr, Andrew, Petrel, Trevor, Petrikovics, Ilona, Rockwood, Gary A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767715/
https://www.ncbi.nlm.nih.gov/pubmed/26861644
http://dx.doi.org/10.1007/s40268-016-0122-3
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author Bartling, Craig M.
Andre, Jon C.
Howland, Carrie A.
Hester, Mark E.
Cafmeyer, Jeffrey T.
Kerr, Andrew
Petrel, Trevor
Petrikovics, Ilona
Rockwood, Gary A.
author_facet Bartling, Craig M.
Andre, Jon C.
Howland, Carrie A.
Hester, Mark E.
Cafmeyer, Jeffrey T.
Kerr, Andrew
Petrel, Trevor
Petrikovics, Ilona
Rockwood, Gary A.
author_sort Bartling, Craig M.
collection PubMed
description Novel cyanide countermeasures are needed for cases of a mass-exposure cyanide emergency. A lead candidate compound is dimethyl trisulfide (DMTS), which acts as a sulfur donor for rhodanese, thereby assisting the conversion of cyanide into thiocyanate. DMTS is a safe compound for consumption and, in a 15 % polysorbate 80 (DMTS-PS80) formulation, has demonstrated good efficacy against cyanide poisoning in several animal models. We performed a stability study that investigated the effect of temperature, location of formulation preparation, and pH under buffered conditions. We found that while the stability of the DMTS component was fairly independent of which laboratory prepared the formulation, the concentration of DMTS in the formulation was reduced 36–58 % over the course of 29 weeks when stored at room temperature. This loss typically increased with increasing temperatures, although we did not find statistical differences between the stability at different storage temperatures in all formulations. Further, we found that addition of a light buffer negatively impacted the stability, whereas the pH of that buffer did not impact stability. We investigated the factors behind the reduction of DMTS over time using various techniques, and we suggest that the instability of the formulation is governed at least partially by precipitation and evaporation, although a combination of factors is likely involved. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-016-0122-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-47677152016-03-29 Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate Bartling, Craig M. Andre, Jon C. Howland, Carrie A. Hester, Mark E. Cafmeyer, Jeffrey T. Kerr, Andrew Petrel, Trevor Petrikovics, Ilona Rockwood, Gary A. Drugs R D Original Research Article Novel cyanide countermeasures are needed for cases of a mass-exposure cyanide emergency. A lead candidate compound is dimethyl trisulfide (DMTS), which acts as a sulfur donor for rhodanese, thereby assisting the conversion of cyanide into thiocyanate. DMTS is a safe compound for consumption and, in a 15 % polysorbate 80 (DMTS-PS80) formulation, has demonstrated good efficacy against cyanide poisoning in several animal models. We performed a stability study that investigated the effect of temperature, location of formulation preparation, and pH under buffered conditions. We found that while the stability of the DMTS component was fairly independent of which laboratory prepared the formulation, the concentration of DMTS in the formulation was reduced 36–58 % over the course of 29 weeks when stored at room temperature. This loss typically increased with increasing temperatures, although we did not find statistical differences between the stability at different storage temperatures in all formulations. Further, we found that addition of a light buffer negatively impacted the stability, whereas the pH of that buffer did not impact stability. We investigated the factors behind the reduction of DMTS over time using various techniques, and we suggest that the instability of the formulation is governed at least partially by precipitation and evaporation, although a combination of factors is likely involved. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-016-0122-3) contains supplementary material, which is available to authorized users. Springer International Publishing 2016-02-09 2016-03 /pmc/articles/PMC4767715/ /pubmed/26861644 http://dx.doi.org/10.1007/s40268-016-0122-3 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research Article
Bartling, Craig M.
Andre, Jon C.
Howland, Carrie A.
Hester, Mark E.
Cafmeyer, Jeffrey T.
Kerr, Andrew
Petrel, Trevor
Petrikovics, Ilona
Rockwood, Gary A.
Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate
title Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate
title_full Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate
title_fullStr Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate
title_full_unstemmed Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate
title_short Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate
title_sort stability characterization of a polysorbate 80-dimethyl trisulfide formulation, a cyanide antidote candidate
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767715/
https://www.ncbi.nlm.nih.gov/pubmed/26861644
http://dx.doi.org/10.1007/s40268-016-0122-3
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