title: Stability and compatibility of topotecan hydrochloride for injection with common infusion solutions and containers.
abstract: The stability and compatibility of topotecan hydrochloride with common infusion solutions and containers were studied. During this study, the leaching of diethylhexyl phthalate (DEHP), a major plasticizer of some polyvinyl chloride (PVC) materials was also investigated. A formulation of topotecan hydrochloride was added to 50 ml PVC infusion bags, polyolefin infusion bags and 150 ml glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection at an initial nominal topotecan concentration of 0.05 mg ml-1. Additionally, the topotecan hydrochloride formulation was added to 50 ml PVC infusion bags containing either 5% dextrose injection or 0.9% sodium chloride injection at an initial nominal topotecan concentration of 0.025 mg ml-1. Containers were maintained at 5 degrees C for 7 days or 23-24 degrees C for 24 h. Samples were analyzed using a stability-indicating HPLC method to determine the concentration of topotecan and the presence of any degradates. The samples were also analyzed by separate HPLC methods to detect the presence of DEHP and the hydrolyzed lactone ring form (SKF 105992) of topotecan hydrochloride. In addition, the pH of each sample was measured initially and at the end of the storage time. There was no significant loss of topotecan observed for any of the conditions studied and no significant increase in degradates was observed. The pH remained unchanged for all samples between the start and end of the study. At the concentrations studied, topotecan hydrochloride was stable for up to 24 h at room temperature and for up to 7 days at 5 degrees C, in PVC and polyolefin infusion bags and glass bottles containing either 5% dextrose injection or 0.9% sodium chloride injection. The presence of topotecan hydrochloride did not contribute to leaching of DEHP in the PVC infusion bags.
authors.affiliation: SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA. samuel_b_craig@sbphrd.com
authors.forename: S B
authors.initials: SB
authors.lastname: Craig
authors.forename: U H
authors.initials: UH
authors.lastname: Bhatt
authors.forename: K
authors.initials: K
authors.lastname: Patel
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004051:Diethylhexyl Phthalate / Q000032:analysis*; D004355:Drug Stability; D005947:Glucose / Q000737:chemistry; D006868:Hydrolysis; D011143:Polyvinyl Chloride / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry; D019772:Topotecan / Q000032:analysis* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D012965:Sodium Chloride; D019772:Topotecan; D011143:Polyvinyl Chloride; D004051:Diethylhexyl Phthalate; D005947:Glucose