Concentration-Dependent Compatibility and Stability of Dexamethasone and Midazolam

Objective: To study the stability and compatibility of dexamethasone 21 phosphate disodium salt and midazolam at various concentrations at 4 C and 23 C. Methods: Solutions of dexamethasone (4 and 10 mg/mL) were mixed with midazolam (1 and 5 mg/mL). In addition to visual inspection of the mixtures, the concentrations of dexamethasone and midazolam in the mixtures were determined by a stability-indicating liquid chromatographic method. Results: Precipitation occurred when equal volumes of the most concentrated solutions were mixed. Some combinations at lower concentrations were compatible on visual inspection and retained 90% of their initial concentrations. Upon dissolution and analysis of the precipitate, the only drug present in the precipitate was midazolam. The stability of a compatible solution of 0.25 mg/mL dexamethasone and 0.25 mg/mL midazolam was tested over a 3-day period at 4 C and 23 C. Physical incompatibility, because of precipitation of midazolam, was observed after 48 h. However, during the first 24 h, both solutions remained clear and free of precipitate and retained 90% of the initial concentration of both dexametha-