The objective of this study was to evaluate the physical and chemical stabilty of undiluted palonosetron hydrochloride 50 micrograms/mL in combination with topotecan hydrochloride 0.1 mg/mL or irinotecan hydrochloride 1 mg/mL in 5% dextrose injection during simulated Y-site administration. Triplicate test samples were prepared by admixing 5 mL of palonosetron hydrochloride with 5 mL of the topotecan hydrochloride or irinotecan hydrochloride admixture. Physical stabilty was assessed by using a multistep evaluation preocdure 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 to determine drug concentrations. Evaluations were performed initially upon mixing and again 1 and 4 hour after mixing. The palonosetron hydrochloride-topotecan hydrochloride samples were clear and pale yellow when viewed in normal fluorescent room light. When viewed with a Tyndall beam, the samples had a slight haziness. The palonosetron hydrochloride-irinotecan hydrochloride samples were clear and colorless when viewed in in normal fluorescent room light and with a Tyndall beam. Measured turbidities remained unchanged; particulate contents were low and changed little. High-performance liquid chromatographic analysis found that palonosetron hydrochloride, topotecan hydrochloride, and irinotecan hydrochloride remained stable throughout the 4-hour test. Little drug loss was observed. Palonosetron hydrochloride is physically compatible and chemically stable with topotecan hydrochloride and with irinotecan hydrochloride during Y-site administration.