Stability of extemporaneously prepared hydroxyurea solutions

Am J Health Syst Pharm. 2024 Dec 16;82(1):74-78. doi: 10.1093/ajhp/zxae210.

Abstract

Purpose: To evaluate the stability of a new, more convenient (<30 minutes for preparation), extemporaneously prepared hydroxyurea solution over 78 days.

Methods: A high-performance liquid chromatography (HPLC) method using a hydrophilic interaction chromatography (HILIC) column was developed and validated to accurately measure the concentration of hydroxyurea directly from solution without the need for chemical derivatization. Hydroxyurea was dissolved in sterile water in less than 5 minutes to yield a 100-mg/mL solution, which was then diluted by an equal volume of ORA-sweet vehicle to yield a 50-mg/mL extemporaneously prepared solution of hydroxyurea. The solution samples were kept at refrigeration (4 °C), room temperature (26 °C), and elevated temperature (40 °C) for 78 days.

Results: The 50-mg/mL solutions of hydroxyurea in a 1:1 mixture of water and ORA-sweet kept at 4 °C and 26 °C showed no significant loss of potency (<2%) after 78 days. The solutions kept at 40 °C showed greater than 10% loss of potency after 28 days.

Conclusion: Extemporaneously compounded hydroxyurea 50-mg/mL solutions prepared in a 1:1 mixture of water and ORA-Sweet and stored in amber polypropylene plastic bottles were stable for at least 78 days at room temperature and under refrigeration.

Keywords: chromatography; dosage forms; drug delivery systems; high performance liquid chromatography; hydroxyurea; pediatrics.

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Drug Compounding* / methods
  • Drug Stability*
  • Drug Storage*
  • Hydroxyurea* / chemistry
  • Pharmaceutical Solutions / chemistry
  • Temperature
  • Time Factors

Substances

  • Hydroxyurea
  • Pharmaceutical Solutions