Compatibility of heparin sodium and morphine sulfate

The compatibility of morphine sulfate and heparin sodium was studied in solutions of deionized water and 0.9% sodium chloride. Crystalline morphine sulfate was reconstituted and heparin sodium 100 or 200 units/mL was added. Duplicate samples with a final volume of 5 mL were prepared and stored at room temperature. Morphine sulfate concentrations were 1, 2, 5, and 10 mg/mL in each diluent with each heparin concentration. Samples were visually inspected immediately after preparation and at 0.5 and 24 hours; pH was tested before adding heparin and at 0.5 and 24 hours. Similar procedures were followed adding morphine to the heparin. Samples containing morphine sulfate 2 and 10 mg/mL were analyzed by high-performance liquid chromatography for morphine concentrations immediately before adding heparin and at 0.5 and 24 hours. Precipitate appeared immediately after the second drug was added in samples containing morphine sulfate 10 mg/mL at both heparin concentrations in the water admixtures. No precipitate formed in any solutions containing morphine concentrations of 5 mg/mL or less nor in any samples containing 0.9% sodium chloride. In both diluents, pH values decreased as morphine sulfate concentrations increased. Morphine sulfate concentrations decreased significantly in water admixtures but not in admixtures prepared with 0.9% sodium chloride solution. Morphine sulfate and heparin sodium are incompatible only at morphine concentrations greater than 5 mg/mL. The incompatibility can be prevented by using 0.9% sodium chloride as the admixture diluent.