Chemical Stability of Ziconotide-Clonidine Hydrochloride Admixtures With and Without Morphine Sulfate During Simulated Intrathecal Administration

ABSTRACT

Objective. To determine the stability of ziconotide–clonidine hydrochloride admixtures with and without morphine sulfate during simulated intrathecal infusion under laboratory conditions at 37°.

Materials and Methods. Admixtures of ziconotide (25 µg/mL) and clonidine hydrochloride (2 mg/mL) with and without morphine sulfate (35 mg/mL) were stored in Medtronic SynchroMed® II pumps at 37°. Pumps were sampled immediately after filling and at four additional time points over the course of 28 (ziconotide–clonidine hydrochloride admixture) or 20 (ziconotide–clonidine hydrochloride–morphine sulfate admixture) days. Drug concentrations were determined using high-performance liquid chromatography.

Results. Ziconotide concentration exceeded 97% of initial at all time points when combined with clonidine alone; statistical evaluation indicated that both ziconotide and clonidine concentrations would remain above 90% of initial for more than 60 days. When compounded with both clonidine and morphine, ziconotide and clonidine concentrations declined; statistical evaluation indicated that the ziconotide concentration was 70% of initial after 20 days, and that clonidine would remain 90% stable for 42 days. Morphine was stable in the presence of ziconotide and clonidine.

Conclusions. A ziconotide-clonidine admixture was 90% stable for 60 days (extrapolated), and a ziconotide-clonidine-morphine admixture was 70% stable for 20 days.