Although the U.S. Food and Drug Administration has not approved the combined use of intrathecal medications, practitioners frequently prescribe combination intrathecal therapy for patients who do not experience adequate analgesia with a single intrathecal agent; however, the chemical stability of an analgesic combination may influence the frequency of pump refills necessary to maintain safe and efective pain control. This investigation was performed to evaluate the chemical stability of admixtures containing 25 mcg/mL ziconotide and either 1000 mcg/mL fentanyl citrate or 1000 mcg/mL sufentanil citrate during simulated intrathecal infusion under laboratory conditions at 37 deg C. Admixtures were prepared from commercial ziconotide (25 mcg/mL) and lyophilized powders of the opioid drugs, sparged with nitrogen to remove dissolved oxygen, and stored in implantable intrathecal pumps at 37 deg C. Samples obtained at various intervals over the course of 40 days were assessed for drug concentrations by using high-performance liquid chromatography. The periods of time that the admixtures retained > or = 90% and > or = 80% of the initial concentrations of each drug (i.e., the 90% and 80% stabilities) were determined by using linear regression and 95% confidence intervals. At study end, ziconotide concentrations averaged 87.5% of the initial concentration in the ziconotide/fentanyl admixture and 89.3% of the initial concentration in the ziconotide/sufentanil admixture; opioid concentrations were unchanged. Ziconotide was 90% stable for 26 days and 80% stable for 58 days (extrapolated) when combined with fentanyl; when combined with sufentanil, ziconotide was 90% stable for 33 days and 80% stable for 68 days (extrapolated). The opioids were stable throughout the study. At the concentrations used in this study, ziconotide/fentanyl and ziconotide/sufentanil admixtures were relatively stable.