Abstract:
The stability of a mixture of methotrexate and dexamethasone sodium phosphate in 0.9% sodium chloride for intrathecal (IT) injection was assessed. To simulate the clinically used concentrations of the admixtures, 2mL of 0.9% sodium chloride was added into each of two vials of methotrexate. Both solution mixtures were then transferred into an intrathecal injector. A vial of dexamethasone sodium phosphate (5mg in 1mL) was subsequently added directly to the injector to obtain a mixture of 2mg/mL methotrexate and 1mg/mL dexamethasone. Subsequently, stability as assessed by visual evaluation of color changes, regular pH monitoring, monitoring of changes in particulate contents and drug concentrations in the admixture, and detection of impurities with HPLC- UV-TOF/MS before and after mixing. The results showed that admixtures were clear, no color changes were observed and the pH value remained stable under normal fluorescent room light. The ≥25-μm and ≥10-μm particulate content levels were low and within specification limits. The concentrations of methotrexate and dexamethasone exhibited no significant changes. Impurity peaks before and after mixing were not increased and no new degradation products were detected after mixing. Methotrexate and dexamethasone sodium phosphate did not affect each other’s stability.
