Physical Compatibility and Chemical Stability of Amphotericin B in Combination with Magnesium Sulfate in 5% Dextrose Injection

Abstract

The physical compatibility and chemical stability of amphotericin B for injection USP (AB) admixed with magnesium sulfate injection USP (MS) in 5% dextrose injection USP (D5W) was evaluated. AB (final concentration of either 40 or 80 μg/mL of solution) and MS (final concentration of 0, 2, or 4 mg/mL of solution) were mixed in glass volumetric flasks containing D5W. AB concentration, as quantitated by high-performance liquid chromatography, and visible admixture clarity were monitored at zero, three, and six hours after combining with MS. At the three-hour observation, visible admixture clarity appeared to decrease in all multiple drug combinations and a clear supernatant began to develop as particulates settled to the bottom of the container. MS (final concentration of 4 or 8 mg/mL of solution) and AB (final concentration of 80 μg/mL of solution) were prepared in two separate intravenous polyvinyl chloride bags of D5W. The solutions were manually set to infuse via gravity for six hours and mix at the y-site of an intravenous administration set. Samples of the mixture were collected from the terminal end of a primary intravenous administration set at zero, two, four, and six hours after beginning the infusions. Each sample appeared visibly clear and maintained an AB concentration of at least 100 percent of the initial admixture concentration. MS and AB mixed in the same container appeared to be physically incompatible. The same admixture appeared to be physically compatible and chemically stable, in terms of AB, when infused as separate solutions mixed at a y-site of an intravenous administration set.