Effect of Freeze-Thawing on the Long-Term Stability of Calcium Levofolinate in 5% Dextrose Stored on Polyolefin Infusion Bags

J Clin Pharm Ther. 2009 Aug;34(4):423-8. doi: 10.1111/j.1365-2710.2009.01043.x.

Abstract

Background: Calcium levofolinate infusions could be prepared in advance by a centralized intravenous additive service (CIVAS) to improve safety and time management.

Objective: To investigate the effect of freezing, microwave thawing and long-term storage at 5 +/- 3 degrees C on the stability of calcium levofolinate in 5% dextrose solution.

Methods: Solutions of 250 mL of 5% dextrose in polyolefin bags (n = 5) containing approximately 400 mg of calcium levofolinate were prepared under aseptic conditions and frozen for 95 days at -20 degrees C. The solutions were then thawed using microwaves and stored at 5 +/- 3 degrees C for 1 month. The calcium levofolinate concentrations were measured by high performance liquid chromatography (HPLC). Visual inspection was performed and pH was measured periodically during the storage at 5 +/- 3 degrees C. Stability of the solution was defined as a concentration remaining superior to 90% of the initial concentration by regression analysis as recommended by the Food and Drug Administration (FDA).

Results: No colour change or precipitation in the solutions was observed. Calcium levofolinate infusions were stable when stored at 5 +/- 3 degrees C during 1 month after freeze-thaw treatment. Throughout this period, the lower confidence limit of the estimated regression line of concentration-time profile remained above 90% of the initial concentration. Slight change in pH values from 6.52 +/- 0.01 to 6.50 +/- 0.01 during storage time did not affect retention time on HPLC and has no clinical consequence, the solutions remaining in the acceptable range for perfusion (4 <or= pH <or= 10).

Conclusion: Under the conditions of this study, calcium levofolinate in 5% dextrose infusion may be prepared, frozen in advance by CIVAS, and then microwave thawed before use. Such treatment extends long-term stability and releases pharmacist's time for major activities such as checking medication order errors.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Drug Packaging
  • Drug Stability
  • Drug Storage
  • Freezing
  • Glucose / chemistry*
  • Hydrogen-Ion Concentration
  • Leucovorin / chemistry*
  • Microwaves
  • Pharmaceutical Vehicles / chemistry
  • Polyenes
  • Regression Analysis
  • Solutions
  • Temperature
  • Time Factors
  • Vitamin B Complex / chemistry*

Substances

  • Pharmaceutical Vehicles
  • Polyenes
  • Solutions
  • Vitamin B Complex
  • PL 732
  • Glucose
  • Leucovorin