title: Physical and chemical stability of reconstituted and diluted dexrazoxane infusion solutions.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Alan L
authors.initials: AL
authors.lastname: Myers
authors.forename: Van A
authors.initials: VA
authors.lastname: Trinh
authors.forename: Jitesh D
authors.initials: JD
authors.lastname: Kawedia
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kramer
authors.forename: Robert S
authors.initials: RS
authors.lastname: Benjamin
authors.forename: Hai T
authors.initials: HT
authors.lastname: Tran
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods; D064730:Dexrazoxane / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D007201:Indicator Dilution Techniques; D007262:Infusions, Intravenous; D019999:Pharmaceutical Solutions / Q000737:chemistry*; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D019999:Pharmaceutical Solutions; D064730:Dexrazoxane
keywords: Dexrazoxane; chemical stability; infusion solutions; physical stability; stability indicating high-performance liquid chromatography