Physical instability of frozen pemetrexed solutions in PVC bags.
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.
Zhang
Yanping
Y
Pharmacy Laboratory, The University of Texas MD Anderson Cancer Center, Houston, USA.
Trissel
Lawrence A
LA
D000970:Antineoplastic Agents / Q000737:chemistry; D004355:Drug Stability; D005615:Freezing; D005947:Glucose / Q000737:chemistry; D005971:Glutamates / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D009391:Nephelometry and Turbidimetry; D010316:Particle Size; D000068437:Pemetrexed; D011143:Polyvinyl Chloride; D012965:Sodium Chloride / Q000737:chemistry
D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D012965:Sodium Chloride; D006147:Guanine; D011143:Polyvinyl Chloride; D005947:Glucose