title: Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate.
abstract: 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.
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA. bartlingc@battelle.org.
authors: Craig M
authors: CM
authors: Bartling
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA.
authors: Jon C
authors: JC
authors: Andre
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA.
authors: Carrie A
authors: CA
authors: Howland
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA.
authors: Mark E
authors: ME
authors: Hester
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA.
authors: Jeffrey T
authors: JT
authors: Cafmeyer
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA.
authors: Andrew
authors: A
authors: Kerr
authors: Battelle Memorial Institute, 505 King Ave, Columbus, OH, 43201, USA.
authors: Trevor
authors: T
authors: Petrel
authors: Sam Houston State University, Huntsville, TX, USA.
authors: Ilona
authors: I
authors: Petrikovics
authors: US Army Medical Research Institute of Chemical Defense (USAMRICD), Aberdeen Proving Ground, MD, USA.
authors: Gary A
authors: GA
authors: Rockwood
mesh_terms: D000931:Antidotes / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003486:Cyanides / Q000737:chemistry*; D004355:Drug Stability; D011136:Polysorbates / Q000737:chemistry*; D013440:Sulfides / Q000737:chemistry*; D013696:Temperature; D013861:Thiocyanates / Q000737:chemistry
chemical_list: D000931:Antidotes; D003486:Cyanides; D011136:Polysorbates; D013440:Sulfides; D013861:Thiocyanates; C054170:dimethyl trisulfide; C031760:thiocyanate