Accelerated stability and bioassay of a new oral α-ketoglutarate formulation for treating cyanide poisoning

AbstractContext: Due to several limitations of existing cyanide antidotes, α-ketoglutarate (α-KG) has been proposed as a promising treatment for cyanide.Objective: This study reports the accelerated stability and bioassay of a new oral α-KG formulation.Materials and methods: Amber-colored PVDF bottles containing 100 ml of 10% α-KG in 70% sorbitol, preservative (sodium methyl paraben and sodium propyl paraben), sweetener (sodium saccharine), flavor (American ice-cream soda and peppermint) and color (tartrazine), at pH 7.0–8.0 were stored in stability chamber (40 ± 2 °C and 75 ± 5% humidity) for 6 months in a GMP compliant facility. Various physical (pH, color, evaporation, extractable volume and clarity), chemical (identification and quantification of active ingredient) and microbiological (total aerobic count) analyses, together with protection studies were carried periodically in mice. Acute toxicity of the formulation and bioavailability of α-KG were assessed in rats at the beginning of the experiment.R...