Stability of atropine sulfate prepared for mass chemical terrorism

Preparedness for chemical terrorism includes the procurement of the appropriate pharmacological antagonists. A large emphasis has been placed on having a sufficient quantity of atropine available to treat patients exposed to acetylcholinesterase inhibitors such as sarin. Severe exposures may necessitate the administration of large amounts of atropine and dictate the need to prepare significant quantities of extemporaneously compounded atropine solution to respond to mass numbers of casualties over the first 24-48 hours postexposure.

The objective of this project was to determine the stability of a 1 mg/mL atropine solution prepared in multidose IV solutions of 0.9% sodium chloride over a 72-hr period stored at varying temperatures.

Atropine sulfate solution 1 mg/mL in 0.9% sodium chloride was prepared from sterile pharmaceutical-grade atropine sulfate powder. Multidose bags of atropine sulfate (100 mL) were stored at controlled temperatures of 4 degrees C to 8 degrees C, 20 degrees C to 25 degrees C, and 32 degrees C to 36 degrees C for 3 days and covered with an amber occlusive cover to minimize exposure to light. Six samples from each bag were drawn at 6, 12, 24, 48, and 72 h after preparation and compared with a time zero control sample. The samples were assayed using United States Pharmacopeia/National Formulary (USP/NF) high-performance liquid chromatography (HPLC) methods for atropine sulfate injection. The USP standard of 95% for atropine sulfate stability was used as the primary endpoint.

Atropine sulfate 1 mg/mL in 0.9% sodium chloride was stable for at least 72hr at 4 degrees C to 8 degrees C (percent initial concentration ranging from 96.5% to 103.4%), 20 degrees C to 25 degrees C (percent initial concentration ranging from 98.7% to 100.2%), and 32 degrees C to 36 degrees C (percent initial concentration ranging from 98.3% to 102.8%). Because the IV bags were protected from light during this study, we recommend this practice after preparing the atropine solution.

The amount of atropine necessary to treat hundreds to thousands of victims of a chemical attack is immense. The extemporaneous preparation of atropine solution from pharmaceutical-grade powder eliminates concerns about the storage of excessive quantities of atropine. A 1 mg/mL solution is stable for at least 3 days, allowing for use during the most critical treatment periods after exposure.