Physical and chemical stability of pemetrexed in infusion solutions.
BACKGROUND
Pemetrexed is a multitargeted, antifolate, antineoplastic agent that is indicated for single-agent use in locally advanced or metastatic non-small-cell lung cancer after prior chemotherapy and in combination with cisplatin for the treatment of malignant pleural mesothelioma not treatable by surgery. Currently, there is no information on the long-term stability of pemetrexed beyond 24 hours.


OBJECTIVE
To evaluate the longer-term physical and chemical stability of pemetrexed 2, 10, and 20 mg/mL in polyvinyl chloride (PVC) bags of dextrose 5% injection and NaCl 0.9% injection.


METHODS
Triplicate samples of pemetrexed were prepared in the concentrations and infusion solutions required. Evaluations for physical and chemical stability were performed initially and over 2 days at 23 degrees C protected from light and exposed to fluorescent light, and over 31 days of storage at 4 degrees C protected from light. 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, with little or no loss of pemetrexed over 2 days at 23 degrees C, protected from light and exposed to fluorescent light, and over 31 days of storage at 4 degrees C, protected from light. The room temperature samples were physically stable throughout the 48 hour test period. However, pemetrexed admixtures developed large numbers of microparticulates during refrigerated storage exceeding 24 hours.


CONCLUSIONS
Pemetrexed is chemically stable for 2 days at room temperature and 31 days refrigerated in dextrose 5% injection and NaCl 0.9% injection. However, substantial numbers of microparticulates may form in pemetrexed diluted in the infusion solutions in PVC bags, especially during longer periods of refrigerated storage. Limiting the refrigerated storage period to the manufacturer-recommended 24 hours will limit particulate formation.
Zhang
Yanping
Y
MD Anderson Cancer Center, The University of Texas, Houston, 77030, USA.
Trissel
Lawrence A
LA
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004340:Drug Contamination; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D005615:Freezing; D005971:Glutamates / Q000008:administration & dosage* / Q000737:chemistry* / Q000528:radiation effects; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects; D007262:Infusions, Intravenous; D008027:Light; D000068437:Pemetrexed; D019999:Pharmaceutical Solutions; D011143:Polyvinyl Chloride; D015203:Reproducibility of Results; D013696:Temperature
D000970:Antineoplastic Agents; D005971:Glutamates; D019999:Pharmaceutical Solutions; D000068437:Pemetrexed; D006147:Guanine; D011143:Polyvinyl Chloride