Sealing Effects on the Storage Stability of the Cyanide Antidotal Candidate, Dimethyl Trisulfide

Abstract

Background: Dimethyl trisulfide (DMTS) is a highly lipid-soluble cyanide (CN) antidote candidate molecule. In prior studies with various US FDA-approved co-solvents, surfactants, and their combinations, aqueous solutions containing 15% polysorbate 80 (Poly80) were found to effectively solubilize DMTS in formulations for intramuscular administration. However, DMTS formulated in 15% aqueous Poly80 solutions showed gradual losses over time when stored in vials with septum-based seals. Objective: The present study tested whether storing DMTS formulations in hermetically sealed glass ampules could mitigate storage losses. Methods: Samples consisted of 1-mL aliquots of a 50 mg/ml stock solution of DMTS in 15% aqueous Poly80. The control samples were stored using a vial-within-a-vial system—the inner and outer vials were sealed respectively, with a snap cap, and with a crimped septum. The hermetically sealed test samples were stored in fire-sealed glass ampules. The DMTS content was measured by HPLC–UV analysis at specific time points over a 100-day period. Results: While the control samples exhibited systematic DMTS losses, no DMTS losses were observed from the test samples stored in hermetically sealed glass ampules over the 100-day testing period. Conclusion: DMTS formulated in 15% aqueous Poly80 solution has excellent stability when stored in fire-sealed glass ampules and thus has the potential to be effectively stored as an intramuscular CN countermeasure for mass casualty scenarios.