Binary Mixtures of Morphine and Furosemide: Compatibility and Stability at Different Concentrations

Objectives: In order to avoid separate injections, admixtures of drugs are frequently used in palliative care settings. There are different factors that can influence the compatibility and stability of the mixture: drug type, concentration, solvent, container, temperature and light. There are some mixtures of drugs with proven stability, but there is lack of evidence about the stability and compatibility of the combination of morphine and furosemide. The purpose is to evaluate the compatibility and stability of two admixtures of morphine and furosemide at two different temperatures (25 degrees C and 37 degrees C). The concentrations of the admixtures are: 3.0 mg/mL-2.0 mg/mL; 1.0 mg/mL-0.6 mg/mL; in NaCl 0.9% stored in elastomeric infusors protected from light. Methods: The samples were prepared and diluted in NaCl 0.9% in elastomeric infusor in triplicate to obtain four different conditions of concentration and/or temperature of storage (concentration: 3.0 mg/mL-2.0 mg/mL, 1.0 mg/mL-0.6 mg/mL of morphine and furosemide respectively; temperature of storage 25 degrees C and 37 degrees C). The concentration of each constituent drug into different mixtures was periodically determined using a HPLC-UV method. The drugs were chromatographed on a C-18 reverse phase column; the mobile phase was acetonitrile-water 40:60 (v/v); flow rate 1.5 mL/min. Morphine and furosemide concentrations were determined at 235 nm by interpolation from the calibration curves prepared at (0, 1, 2, 3, 7, 8, 9, 10, 14, 15) days from the standards. Statgraphics centurion XVI program has been used to data treatment. Results: The stability of the admixtures diluted in NaCl 0.9% are as follow: morphine-furosemide (3.0 mg/mL-2.0 mg/mL) is stable (retained > 95% of their initial concentration) eight days at 25 degrees C and two day at 37 degrees C; (1.0 mg/mL-0.6 mg/mL) is stable thirty days at 25 degrees C and two day at 37 degrees C. Conclusion: The admixture of morphine and furosemide in NaCl 0.9% in elastomeric infusor can be safely used in palliative care for at least two days. Concentrations of the admixture can be prepared in advance and stored at room temperature, but the infusion cannot be longer than two days.