Stability of irinotecan hydrochloride in aqueous solutions.

The stability of irinotecan after reconstitution in several vehicles for i.v. infusion was studied. Irinotecan hydrochloride injection was diluted in phosphate buffer solution (pH 4.0, 6.0, and 7.4), 5% dextrose injection, and 0.9% sodium chloride injection to a final concentration of 20 micrograms/mL. The solutions were stored at 25, 37, and 50 degrees C and assayed at intervals up to 24 hours by high-performance liquid chromatography for the concentration of the lactone form of irinotecan remaining. The effect of temperature and pH on the extent and rate of degradation of irinotecan was determined. The hydrolysis of irinotecan to its carboxylate form was reversible. The rate and extent of hydrolysis increased with increasing pH. The use of a weakly acidic vehicle, such as 5% dextrose injection, for reconstitution of irinotecan may maintain the drug's stability prior to administration.