Stability of midazolam hydrochloride in parenteral nutrient solutions

The compatibility and stability of midazolam hydrochloride in three parenteral nutrient (PN) solutions and the stability of 15 amino acids in the presence of midazolam hydrochloride were studied. Six combinations of three PN solutions with amino acid concentrations of 1.5%, 2.5%, and 5% and two midazolam concentrations (0.1 and 0.5 mg/mL) were prepared in triplicate and stored at room temperature under normal fluorescent lighting. Duplicate samples were visually inspected for color change, precipitation, or gas formation and tested for pH. The samples were evaluated for midazolam and amino acid content by high-performance liquid chromatography at zero, one, three, and five hours. Midazolam and amino acid concentrations did not change significantly during the study. There was no evidence of color change, precipitation, or gas formation with any midazolam-PN solution combination when the combinations were examined visually and under a microscope, and no substantial changes in pH occurred. Midazolam 0.1 and 0.5 mg/mL (as the hydrochloride salt) was stable in the three PN solutions studied; in addition, the amino acids present in the 1.5%, 2.5%, and 5% amino acid PN solutions were stable when combined with midazolam at concentrations of 0.1 and 0.5 mg/mL.