Cyanide antidote kit4/2/2023 ![]() ![]() With the single crimp-sealed method, the F2-formulated DMTS was stable for only 2 days and about 60% (M/M) of the original DMTS content was lost after 1 week. (14) reported the effects of three different storage methods of the earlier developed DMTS formulation (F2-formulated DMTS), which included the single crimp-sealed method, the double crimp-sealed method, and the hermetically fire-sealed glass ampule method. Storage methods are one of the contributing factors to the stability of a drug during the drug development process. (5) Lower doses of CN result in dizziness, headache, vomiting, and nausea due to the inhibition of cellular enzymes. For example, induction of pulmonary and coronary arteriolar vasoconstriction can cause pulmonary edema or cardiogenic shock. High doses of CN (>5× LD 50) are capable of producing more adverse responses. Critically, HCN can easily penetrate through the cellular and subcellular membranes. HCN is a weak acid with a p K a of 9.2 therefore, HCN is the dominant form in the human body at pH 7.4. (4) Depending on the pH, CN can be present as the molecular form, hydrogen cyanide (HCN), or as an anion (CN –). ![]() At high enough doses, this results in cell death. When CN enters the mitochondria of living cells, it binds to the terminal enzyme of the electron transport chain, cytochrome c oxidase, resulting in acute cellular hypoxia which prevents the production of ATP. (3) Exposure to CN may cause severe illness or death. Possible intoxication routes include inhalation, dermal absorption, ingestion, or other parenteral administration. (1,2) CN is a very toxic agent, which prevents cells from utilizing oxygen. CN is used in electroplating, in gold and silver mining, and as a nickel aluminum battery constituent. The word “cyanide” (CN) originated from the Greek word kyanos, meaning dark blue. Furthermore, at 4 and 22 ☌, 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 ☌. 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 ☌ and those of disproportionation reactions. Dimethyl disulfide was also observed as a product of degradation, which was further oxidized to S-methyl methanethiosulfonate only when mCPBA was used. Dimethyl tetrasulfide and dimethyl pentasulfide were observed as products using both of the oxidizing agents. To identify the unknown peaks at 37 ☌, controlled oxidation studies were performed on DMTS using two strong oxidizing agents: meta-chloroperoxybenzoic acid ( mCPBA) and hydrogen peroxide (H 2O 2). At 37 ☌, 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. No measurable loss of DMTS was found at 4 and 22 ☌, and good stability was noted up to five months for samples stored at 37 ☌. ![]() ![]() 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. The F3-formulated DMTS was stored in glass ampules at 4, 22, and 37 ☌. This study reports the long-term storage stability of a formulation of the cyanide (CN) antidote dimethyl trisulfide (DMTS). ![]()
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