1. Stability of Diazepam Solution for Injection Following Long-Term Storage in an Ambient Temperature of the Mediterranean Climate.
- Author
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Itin C, Liani M, Zur M, and Gorenbein P
- Subjects
- Animals, Antidotes administration & dosage, Benzophenones administration & dosage, Benzophenones chemistry, Benzophenones toxicity, Diazepam administration & dosage, Diazepam toxicity, Drug Stability, Drug Storage standards, Female, Gas Poisoning etiology, Hot Temperature adverse effects, Humans, Injections, Intravenous, Israel, Male, Models, Animal, Rats, Time Factors, Toxicity Tests, Acute, Antidotes chemistry, Chemical Terrorism, Diazepam chemistry, Gas Poisoning drug therapy, Nerve Agents toxicity
- Abstract
Purpose: Diazepam is utilized as a convulsion antidote following nerve gas attacks. As an emergency medicine, it requires storage at ambient temperatures which often doesn't meet manufacturers' requirements, leading to an early invalidation of the product. Current work investigated this issue., Methods: Long-term stability of diazepam ampoules for injection stored in an ambient temperature of the Mediterranean climate for ~10 years vs storage at room temperature was studied., Results: Diazepam assay and pH remained within pharmacopeial specifications irrespective of storage conditions. A major degradation product 2-methylamino-5-chlorobenzophenone (MACB) showed a clear trend of accumulation as a function of storage time, exceeding the permitted limit at ~2 years, irrespective of storage conditions. A strong correlation between the discoloration of the solutions and the concentration of MACB was obtained. Intravenous administration of MACB to rats at doses ~2200-fold higher than permissible specification levels caused neither mortality nor any toxicological nor post-mortem findings., Conclusions: Regarding the parameters tested: diazepam assay, MACB assay, and pH, storing ampoules of diazepam solution for injection in field conditions of high temperatures of the Mediterranean climate did not cause accelerated degradation as compared to room temperature. These findings open an option for the usage of expired ampoules in special scenarios.
- Published
- 2021
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