1. Evaluation of the Long-Term Storage Stability of the Cyanide Antidote: Dimethyl Trisulfide and Degradation Product Identification.
- Author
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Warnakula IK, Ebrahimpour A, Li SY, Gaspe Ralalage RD, Hewa-Rahinduwage CC, Kiss M, Rios CT, Kelley KD, Whiteman AC, Thompson DE, Rockwood GA, and Petrikovics I
- Abstract
This study reports the long-term storage stability of a formulation of the cyanide (CN) antidote dimethyl trisulfide (DMTS). The F3-formulated DMTS was stored in glass ampules at 4, 22, and 37 °C. Over a period of one year, nine ampules ( n = 3 at each temperature) were analyzed by high-performance liquid chromatography (HPLC)-UV/vis at daily time intervals in the first week, weekly time intervals in the first month, and monthly thereafter for a period of one year to determine the DMTS content. No measurable loss of DMTS was found at 4 and 22 °C, and good stability was noted up to five months for samples stored at 37 °C. At 37 °C, a 10% (M/M) decrease of DMTS was discovered at the sixth month and only 30% (M/M) of DMTS remained by the end of the study; discoloration of the formulation and the growth of new peaks in the HPLC chromatogram were also observed. To identify the unknown peaks at 37 °C, controlled oxidation studies were performed on DMTS using two strong oxidizing agents: meta -chloroperoxybenzoic acid ( m CPBA) and hydrogen peroxide (H
2 O2 ). Dimethyl tetrasulfide and dimethyl pentasulfide were observed as products using both of the oxidizing agents. Dimethyl disulfide was also observed as a product of degradation, which was further oxidized to S -methyl methanethiosulfonate only when m CPBA was used. HPLC-UV/vis and gas chromatography-mass spectrometry/solid phase microextraction analysis revealed good agreement between the degradation products of the stability study at 37 °C and those of disproportionation reactions. Furthermore, at 4 and 22 °C, chromatograms were remarkably stable over the one-year study period, indicating that the F3-formulated DMTS shows excellent long-term storage stability at T ≤ 22 °C., Competing Interests: The authors declare the following competing financial interest(s): Two patents by two coauthors, related to DMTS are: (1) Gary A. Rockwood, Ilona Petrikovics (SHSU) and Steven I. Baskin (USAMRICD): Dimethyl Trisulfide as a Cyanide Antidote. U.S. Patent No. 9,375,407, 2016, (2) Ilona Petrikovics and Kristof Kovacs (SHSU). Formulations of Dimethyl Trisulfide for Use as a Cyanide Antidote. U.S. Patent No. 9,456,996, 2016., (© 2020 American Chemical Society.)- Published
- 2020
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