admixture

Roy and Hildgren studied the stability of admixtures of ketamine and morphine at concentrations of 1, 10, and 25 mg/mL, packaged in PVC bags, syringes, and medication cassette reservoirs and found the combination to be stable for 6 days at room temperature. The current study extends the expiry date to 91 days for the combinations of ketamine and morphine most commonly used at the author’s institution. The effects of storage at 5°C and of exposure to light were also determined. There was no apparent change in stability when syringes were stored at 5°C or when they were exposed to light. The variation in concentration of morphine did not seem to affect the compatibility or stability of the mixture.

At the pH values of the mixtures studied, ketamine and morphine exist predominantly in their cationic or ionized acid forms, according to the practically equal pKa values of 7.5 and 8.0, respectively. Thus, the lack of precipitation in the mixtures was expected. Similarly, oxidation of the phenolic hydroxyl group of morphine was not expected at the acidic pH values of the mixtures.

Degradation products were adequately separated from the internal standard and from each of the parent compounds. Both ketamine and morphine were more stable under acidic conditions, whereas alkaline conditions caused more destruction of both drugs. The extent of degradation under harsh oxidative conditions suggested that both agents are somewhat sensitive to oxidation.
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Admixtures of ketamine (2 mg/mL) and morphine (2, 5, or 10 mg/mL) were physically compatible and retained greater than 98% of their initial concentration after 91 days of storage at either 23°C with exposure to light or 5°C with protection from light when diluted with normal saline and packaged in polypropylene syringes. Verification of aseptic technique and testing of sterility of finished products should be performed before this extended expiry date is implemented in practice.