Physical compatibility and chemical stability of ketamine-morphine mixtures in polypropylene syringes

Abstract

Background: Small amounts of ketamine administered with a narcotic can help to reduce both requirements for and potential adverse effects of the opioid. The use of ketamine in conjunction with morphine has become popular with the Acute Pain Service of the author's hospital. However, the only reported stability data that have been found for this combination stored in syringes were for 6 days at room temperature. Objective, To conduct a compatibility and stability study with the ultimate aim of extending the current expiry date for the concentrations of ketamine and morphine combinations used at the author's institution and thus to allow batch production of mixtures of these drugs without increasing wastage. Methods: Commercial solutions of ketamine (50 mg/mL) and morphine sulphate (50 mg/mL) were combined and further diluted with 0.9% sodium chloride to final concentrations of ketamine 2 mg/mL and morphine 2, 5, or 10 mg/mL; the resulting mixtures were packaged in polypropylene syringes. The syringes were stored at either 23°C or 5°C for 91 days. The following physical compatibility parameters were monitored: clarity, colour, and pH. Chemical stability was determined with a validated stability-indicating high-performance liquid chromatography system. Results: Over the 91 days, all solutions remained dear and colourless, and the pH did not change significantly. The concentration of each drug in the various solutions remained above 98% of the original concentration for both storage conditions for the duration of the study. Conclusions: Solutions of ketamine (2 mg/mL) combined with morphine (2, 5, or 10 mg/mL) were physically compatible and chemically stable for 91 days when diluted with normal saline, packaged in polypropylene syringes, and stored at either 23°C or 5°C.