Analysis and Stability of Deferoxamine and Hydrocortisone Admixtures

P. Yuan, N. U. Aigbogun1, C. Chamberlain, R. DeChristoforo, G. J. Grimes, G. K. Potti
National Institutes of Health

Purpose: Deferoxamine (DEF) is a chelating agent used to remove excess iron load from patients with sickle cell disease due to frequent blood transfusion to alleviate anemia. Common complaints with DEF infusions are redness, swelling, tenderness and pain at the site of the subcutaneous catheter. Hydrocortisone (HYD) is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema or topically for allergic rashes. The admixture of DEF and HYD has been given to patients as one of the alternatives for reducing the inflammations. This combination has been in clinical use, however, no published studies indicate that the combination is stable. The purpose of this study is to see if the combinations are stable for up to seven days.

Methods: The admixtures of DEF/HYD were prepared at concentration of 250 mg/ml DEF/1 mg/ml HYD (A) and 100 mg/ml DEF/1 mg/ml HYD (B) (all base drug equivalent) and stored in 60 cc monoject syringes at room temperature. Stability of the drug
admixtures was followed by visual observation, pH testing, USP chelating UV assay on DEF and Optical Rotation analysis on HYD. In addition, a stability-indicating HPLC assay has been developed to test DEF and HYD together.

Results: Both (A) and (B) solutions are visually clear, no precipitation over the 7 days period. The pH values of the solution are 5.1 +/- 0.1 for (A) and 5.46 +/- 0.08 for (B), contents of DEF and HYD are above 98% relative to initial testing over the seven days period from our preliminary analysis using UV and OR. Both DEF and HYD would degrade when subject to high temperature, acidic and alkali conditions and with the presence of hydrogen peroxide. The degradation products were well
resolved from DEF and HYD in the chromatograms. Stability-indicating HPLC analysis of the drug admixtures is in progress.

Conclusion: The admixtures of DEF and HYD are stable at controlled room temperature for at least seven days

Reference: . Referência: Yuan P, Aigbogun NU, Chamberlain C, DeChristoforo R, Grimes GJ, Potti GK. Analysis and Stability of Deferoxamine and Hydrocortisone Admixtures. Disponível em: http://www.aaps.org/abstracts Acesso em: 04 de agosto de 2010