Physical Compatibility and Chemical Stability of a Concentrated Solution of Atropine Sulfate (2 mg/mL) for Use as an Antidote in Nerve Agent Casualties.

Atropine is one of the preferred antidotes for nerve gas exposure. Effective therapy requires large doses. Stockpiling of atropine in forms currently available commercially can be costly and can require a large storage area. Other problems in using the commercial product are the time required to break the large number of ampules needed for treatement, and the large volume of medication that must be administered. A preparation of concentrated atropine for injection from atropine powder is the ideal solution, but the stability of this preparation is unknown. A formulation for concentrated atropine sulfate solution (2 mg/mL) was developed using pharmaceutical-grade powder. The solution was prepared in isotonic saline solution and packaged in polypropylene syringes, which were sealed with syringe caps. Assessment of physical stability under several storage conditions was based on clarity, color, and pH monitoring. Chemical stability of the preparation was determined by using a stability-indicating high-performance liquid chromatographic method. All solutions remained clear and colorless, and the pH changed only slightly over the study period. The potency of the atropine sulfate solution remained above the United States Pharmacopeia limit of 93% for the duration of the study. The solutions were physically compatible and chemically stable when stored for 28 days at 35 deg C and exposed to light, 364 days at 23 deg C and exposed to light, or 364 days at 5 deg C and protected from light. Concentrated solutions of atropine sulfate can be compounded quickly and easily by using commercially available pharmaceutical-grade powder as the active ingredient. The extended shelf-life allows the preparation to be readily available in the field as required.