Physical instability of frozen pemetrexed solutions in PVC bags

Ann Pharmacother. Jul-Aug 2006;40(7-8):1289-92. doi: 10.1345/aph.1G558. Epub 2006 Jul 5.

Abstract

Background: Pemetrexed is a multitargeted antifolate antineoplastic agent indicated for single-agent use in advanced or metastatic non-small-cell lung cancer and in combination with cisplatin for the treatment of malignant pleural mesothelioma not treatable by surgery. Currently, there is no information on the stability of frozen pemetrexed solutions.

Objective: To evaluate the stability of pemetrexed admixtures in common infusion solutions frozen at -20 degrees C to determine the drug stability period up to 90 days.

Methods: Triplicate samples of pemetrexed were prepared in concentrations of 2, 10, and 20 mg/mL in dextrose 5% and NaCl 0.9% injection in polyvinyl chloride (PVC) bags. Evaluations for physical and chemical stability were performed initially and over 90 days of frozen storage. Physical stability was assessed using turbidimetric and particulate measurement as well as visual observation. Chemical stability was evaluated by HPLC.

Results: All pemetrexed solutions remained chemically stable throughout the 90 day study period, with little or no loss of pemetrexed. However, the pemetrexed admixtures in PVC bags developed large numbers of microparticulates during long-term frozen storage.

Conclusions: Although pemetrexed is chemically stable for 90 days frozen at -20 degrees C, substantial numbers of microparticulates formed in pemetrexed diluted in the infusion solutions in PVC bags upon long-term frozen storage. The avoidance of freezing pemetrexed solutions in PVC bags is therefore warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Drug Stability
  • Freezing
  • Glucose / chemistry
  • Glutamates / chemistry*
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Nephelometry and Turbidimetry
  • Particle Size
  • Pemetrexed
  • Polyvinyl Chloride
  • Sodium Chloride / chemistry

Substances

  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Sodium Chloride
  • Guanine
  • Polyvinyl Chloride
  • Glucose