Physical and chemical stability of reconstituted and diluted dexrazoxane infusion solutions

Abstract

Background and purpose Dexrazoxane is used clinically to prevent anthracycline-associated cardiotoxicity. Hydrolysis of dexrazoxane prior to reaching the cardiac membranes severely hampers its mode of action; therefore, degradation during the preparation and administration of intravenous dexrazoxane admixtures demands special attention. Moreover, the ongoing national shortage of one dexrazoxane formulation in the United States has forced pharmacies to dispense other commercially available dexrazoxane products. However, the manufacturers’ limited stability data restrict the flexibility of dexrazoxane usage in clinical practice. The aims of this study are to determine the physical and chemical stability of reconstituted and diluted solutions of two commercially available dexrazoxane formulations. Methods The stability of two dexrazoxane products, brand and generic name, in reconstituted and intravenous solutions stored at room temperature without light protection in polyvinyl chloride bags was determined. The concentrations of dexrazoxane were measured at predetermined time points up to 24 h using a validated reversed phase high-performance liquid chromatography with ultraviolet detection assay. Results Brand (B-) and generic (G-) dexrazoxane products, reconstituted in either sterile water or 0.167 M sodium lactate (final concentration of 10 mg/mL), were found stable for at least to 8 h. Infusion solutions of B-dexrazoxane, prepared according to each manufacturer’s directions, were stable for at least 24 h and 8 h at 1 mg/mL and 3 mg/mL, respectively. Infusion solutions of G-dexrazoxane, prepared in either 5% dextrose or 0.9% sodium chloride following the manufacturer’s guidelines, were also stable for at least 24 h and 8 h at 1 mg/mL and 3 mg/mL, respectively. All tested solutions were found physically stable up to 24 h at room temperature. Conclusion The stability of dexrazoxane infusion solutions reported herein permits advance preparation of dexrazoxane intravenous admixtures, facilitating pharmacy workflow and clinical operations. However, due to the potential risks of fluid overload when these intravenous solutions are administered to patients, caution is advised to ensure patient safety.