title: 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.
authors.affiliation: Elan Pharmaceuticals Inc., South San Francisco, CA, USA;              Gilead Inc., Foster City, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Shields
authors.forename: Rick
authors.initials: R
authors.lastname: Montenegro