Stability of three cytotoxic drug infusions in the Graseby 9000 ambulatory infusion pump

Abstract

Objective. The purpose of this study was to deter mine the stability of three cytotoxic infusions in the Graseby 9000 ambulatory pump (Graseby Medical, Watford, UK) under both refrigerated storage and in-use conditions. The infusions studied were: (a) doxorubicin (2 mg/mL) plus vincristine (0.2 mg/mL) and (b) ifosfamide (20 mg/mL) plus mesna (20 mg/ mL) and etoposide (0.5 mg/mL). In each case, the diluent was water for injection.

Methods. Graseby 9000 medication cassettes, each containing one of three infusions studied, were incubated at either 8°C or 37°C to represent refriger ated storage or 'in-use' temperatures, respectively. Samples were withdrawn for chemical and physical analysis at various intervals. Chemical stability was determined using validated, stability-indicating high performance liquid chromatography methods. The assessment of physical stability included pH, appear ance, moisture loss from cassettes, subvisual particu late counts, and leaching of diethylhexylphthalate (DEHP) plasticiser from the medication cassettes.

Results. Both the doxorubicin plus vincristine and the ifosfamide plus mesna infusions were physi cally and chemically stable in Graseby 9000 medica tion cassettes for 14 days at 8°C and for 7 days at 37°C. The etoposide infusion caused significant leach ing of DEHP plasticiser from the Graseby cassette; in addition, one of the infusion cassettes stored at 8°C exhibited precipitation of etoposide by day 10.

Conclusion. Infusions of doxorubicin (2 mg/ mL) plus vincristine (0.2 mg/mL) and ifosfamide (20 mg/mL) plus mesna (20 mg/mL) demonstrated ac ceptable stability in the Graseby 9000 device under refrigerated storage and ambulatory infusion condi tions. Precipitation under refrigerated storage and significant leaching of DEHP would preclude the combination of etoposide infusion (0.5 mg/mL) and the Graseby 9000 pump for ambulatory administra tion.