Chemical Stability of Admixtures Containing Ziconotide 25 mcg/mL and Morphine Sulfate 10 mg/mL or 20 mg/mL During Simulated Intrathecal Administration.

The chemical stability of an intrathecally administered analgesic combination may influence the frequency of pump refills necessary to maintain safe and effective analgesia. Previous work has shown that the stability of ziconotide at body temperature is reduced substantially by the presence of morphine sulfate 35 mg/mL. The current study was performed to evaluate the chemical stability of admixtures combining ziconotide with lower concentrations of morphine sulfate during simulated intrathecal infusion under laboratory conditions at 37 deg C. Admixtures containing ziconotide 25 mcg/mL and morphine sulfate 10 mg/mL or 20 mg/mL were stored in implantable intrathecal pumps at 37 deg C and in control vials at 37 deg C or 5 deg C. Samples were obtained over 60 days (admixture containing morphine sulfate 10 mg/mL) or 28 days (admixture containing morphine sulfate 20 mg/mL) and drug concentrations were assessed by high-performance liquid chromatography. Estimates of the time intervals that each admixture retained > or= 90% and > or = 80% of the initial concentrations of both drugs (i.e., the 90% and 80% stabilites) were based on 95% confidence bounds obtained via linear regression. Morphine sulfate 10 mg/mL, the mean ziconotide concentration declined to 81.4% of the initial concentration in 60 days, and 90% and 80% stabilites were maintained for 34 days and 65 days, respctively. In the admixture containing morphine sulfate 20 mg/mL, the mean ziconotide concentration declined to 85.3% of the initial concentration in 28 days, and 90% and 80% stabilities were maintained for 19 days and 37 days, respectively. Decreasing the concentration of morphine in an admixture containing ziconotide improves the stablity of ziconotide.