Stability of azacitidine in infusion fluids

Abstract

The stability of azacitidine in four infusion fluids was studied. Azacitidine was reconstituted and diluted to final concentrations of 0.2 mg/ml and 2.0 mg/ml in glass bottles and plastic i.v. bags containing 0.9% sodium chloride injection, 5% dextrose injection, lactated Ringer's injection, or Normosol -R. All admixtures containing azacitidine 2.0 mg/ml and both drug concentrations in Normosol -R were prepared in glass bottles only. The pH of each solution was measured before mixing, immediately after mixing, and after six hours. Duplicate samples of each solution were removed for assay by high-performance liquid chromatography at zero time, then at hourly intervals for six hours, and again at 25 hours. Three experimental runs were performed for each combination of drug concentration, infusion fluid, and type of container. The percentage of initial (zero time) concentration remaining was determined and plotted versus time. This plot was used to calculate the t90 (time at which 90% of the initial concentration remained) for each solution. The t90 values did not exceed three hours for any of the solutions studied. At the 0.2 mg/ml concentration, the t90 value in 5% dextrose injection (0.8 hours) was much smaller than that of the other solutions, which had t90 values of about two hours. In plastic bags, the percentage of initial azacitidine concentration remaining after six hours was less in 5% dextrose injection than in any other solution. The t90 values for all solutions containing azacitidine 2.0 mg/ml were similar, ranging from 2.4 to 3.0 hours.(ABSTRACT TRUNCATED AT 250 WORDS)