Compatibility of butorphanol with granisetron in 0.9% sodium chloride injection packaged in glass bottles or polyolefin bags

Abstract

The stability of admixtures containing butorphanol and granisetron in polyolefin bags and glass bottles stored at 4 and 25 °C was studied. Commercial solutions of butorphanol tartrate and granisetron hydrochloride were combined and further diluted with 0.9% sodium chloride injection to final concentrations of butorphanol tartrate 0.08 mg/mL and granisetron 0.03 or 0.06 mg/mL; the resulting mixtures were packaged in polyolefin bags and glass bottles. The admixtures were assessed for periods of up to 48 hours after storage at 25 °C without protection from room light and up to 14 days at 4 °C with protection from room light. The chemical stability of the admixtures was evaluated by a validated high-performance liquid chromatography (HPLC) method and by measurement of pH values. Solution appearance and color were assessed by observing the samples against room light and dark backgrounds. HPLC analysis demonstrated that the percentages of the initial concentrations of butorphanol and granisetron in the various solutions remained above 97% during the testing period. No changes in color or turbidity were observed in any of the prepared solutions. Throughout this period, pH values remained stable. Admixtures of butorphanol tartrate 0.08 mg/mL and granisetron 0.03 or 0.06 mg/mL in 0.9% sodium chloride injection in polyolefin bags or glass bottles remained stable for 48 hours when stored at 25 °C exposed to room light and for 14 days when stored at 4 °C protected from room light.