Physical and chemical stability of palonosetron with metoclopramide and promethazine during simulated y-site administration.

ABSTRACT

The objective of this study was to evaluate the physical and chemical stability of mixtures of undiluted palonosetron hydrochloride 50 micrograms/mL with undiluted metoclopramide hydrochloride 5 mg/mL and with promethazine hydrochloride 2 mg/mL diluted in 5% dextrose injection during simulated Y-site administration. Triplicate test samples were prepared by admixing 7.5 mL of palonosetron hydrochloride with 7.5 mL of the undiluted metoclopramide hydrochloride and, separately, with the promethazine hydrochloride dilution. Physical stability was assessed using a multistep evaluation procedure that included both turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by using stability-indicating high-performance liquid chromatographic analytical techniques based on the determination of drug concentrations. Evaluations were performed initially upon mixing and 1 and 4 hours after mixing. The samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidities remained unchanged; particulate contents were low and exhibited little change. High-performance liquid chromatographic analysis revealed that palonosetron hydrochloride and both metoclopramide hydrochloride and promethazine hydrochloride remained stable throughout the 4-hour test with no drug loss. Palonosetron hydrochloride is physically compatible and chemically stable with undiluted metoclopramide hydrochloride and also with promethazine hydrochloride diluted in 5% dextrose injection during simulated Y-site adminstration.