Chemical Stability of Admixtures Combining Ziconotide with Morphine or Hydromorphone During Simul ated Intrathecal Administration.

Objective.  To determine the stability of admixtures combining ziconotide with morphine or hydromorphone under simulated intrathecal infusions. Materials and Methods.  Admixtures of ziconotide (25 µg/mL) with morphine or hydromorphone (both at 35 mg/mL) were stored in Medtronic SynchroMed® II pumps at 37°C, and in control vials at 37°C and 5°C. Drug concentrations were determined using high-performance liquid chromatography. Results.  The ziconotide pump concentration with morphine declined to 79% of initial in 17 days, and to 88% of initial after 25 days with hydromorphone. Ziconotide concentrations in control vials stored at 37°C displayed similar rates of decay, but vials stored at 5°C exhibited no ziconotide loss. A statistical evaluation of the two combinations shows ziconotide-hydromorphone retaining 80% stability for 40 days (extrapolated), compared to 15 days for ziconotide-morphine. Morphine and hydromorphone were stable in the presence of ziconotide under all conditions. Conclusions.  Ziconotide-hydromorphone admixtures were more stable than ziconotide-morphine admixtures.