Stability of dilutions of methadone alone, and in combination with lidocaine and ketamine.

OBJECTIVES

To assess stability and degradation over time, of methadone alone, and mixed with lidocaine and ketamine, using various diluents and storage conditions.

MATERIALS AND METHODS

Solutions of methadone diluted in 0.9% NaCl, and methadone-lidocaine-ketamine diluted in 0.9% NaCl or Hartmann's solution, and stored at room temperature with exposure to light, or refrigerated at 4°C and protected from light, were maintained over 10 days. Chemical stability was determined using liquid chromatography immediately after preparation and following 4, 24, 48, 96 and 240 hours of storage. Physical stability of the solutions was evaluated by visual examination and absorbance of ultraviolet/visible light. A linear model assessed the impact of different diluent solutions and storage conditions on drug degradation over time.

RESULTS

There was no evidence of physicochemical incompatibility for any solution. Methadone concentration, when diluted alone or in methadone-lidocaine-ketamine with Hartmann's solution at 4°C, did not decline over time. Ketamine and lidocaine decreased to a similar extent over time, regardless of the diluent used or storage method, while methadone in methadone-lidocaine-ketamine diluted with 0.9% NaCl or with Hartmann's solution at room temperature exposed to light, also declined over time; however, all three methadone-lidocaine-ketamine components retained acceptable stability (<10% degradation) for at least 48 hours following preparation, irrespective of diluent or storage conditions.

CLINICAL SIGNIFICANCE

Regardless of the diluent or storage method, methadone-lidocaine-ketamine solutions degrade over time, but this only becomes clinically significant after 48 hours. Solutions of 1 mg/ml methadone in 0.9% NaCl are stable for at least 10 days under storage conditions likely to be encountered in general practice.