Aarau, CH-5001 h r a u , Switzerland
SUMMARYThe stability of a preservative-free morphine chloride solution for intravenous or intrathecal use manufactured at a concentration of 40 mglml, near the solubility limit in water, was studied. The influence of heat and oxygen on morphine content was measured with and without autoclaving, and after additional thermal and oxidative stress. The morphine injection was stable during steam sterilization at 121°C for up to I80 min if the solution was adjusted to a pH of 3. High-performance liquid chromatography with W detection (HPLC) and direct W spectroscopy (W) (the latter available in most hospital pharmacies for analytical purposes) were compared for specificity, precision and appropriateness for content and stability assessment of morphine solutions. UV could only be used for quantification of undecomposed morphine. Morphine degradation products of stressed solutions interfered with the direct W assay of morphine at 286 nm, whereas these interfering components were separated by the ion-pair reversed-phase HPLC used. The results demonstrate that even in the absence of stabilizers, morphine chloride solutions may safely be sterilized for 15 min at 121°C. The HPLC method was shown to be sufficiently sensi-