Stability, potency, and preservative effectiveness of epoetin alfa after addition of a bacteriostatic diluent

Am J Hosp Pharm. 1992 Jun;49(6):1455-8.

Abstract

The stability, potency, and preservative effectiveness of two dilutions of epoetin alfa containing a bacteriostatic diluent were studied. Epoetin alfa 10,000 units/mL in single-use vials was diluted 1:1 and 1:1.5 with bacteriostatic 0.9% sodium chloride injection. USP tests of preservative effectiveness were performed on samples from two batches each of the 1:1 and the 1:1.5 dilutions. Appearance assessment, Western blot analysis, radioimmunoassay, and bioassay were used to determine the stability or potency of samples from three batches of each dilution that were stored at 5 degrees C or at 30 degrees C for 12 weeks. Both batches of the 1:1.5 dilution (epoetin alfa 4,000 units/mL with 0.54% benzyl alcohol) met the USP criteria for preserved solutions, while one batch of the 1:1 dilution (epoetin alfa 5,000 units/mL with 0.45% benzyl alcohol) did not. Epoetin alfa 10,000 units/mL diluted either 1:1 or 1:1.5 with bacteriostatic 0.9% sodium chloride injection and stored at 5 degrees C or at 30 degrees C remained stable and potent for 12 weeks. The addition of 1.5 mL of bacteriostatic 0.9% sodium chloride injection to a vial containing 1 mL of epoetin alfa 10,000 units/mL makes a solution of epoetin alfa 4,000 units/mL that meets the USP criteria for preservative effectiveness and remains stable and potent for 12 weeks at 5 degrees C.

MeSH terms

  • Animals
  • Blotting, Western
  • Drug Incompatibility
  • Drug Stability
  • Erythrocytes / metabolism
  • Erythropoietin / blood
  • Erythropoietin / chemistry*
  • Erythropoietin / pharmacology
  • Iron / blood
  • Mice
  • Preservatives, Pharmaceutical
  • Radioimmunoassay
  • Recombinant Proteins / blood
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacology
  • Sodium Chloride / pharmacology

Substances

  • Preservatives, Pharmaceutical
  • Recombinant Proteins
  • Erythropoietin
  • Sodium Chloride
  • Iron