title: Long-term stability study of clofarabine injection concentrate and diluted clofarabine infusion solutions.
abstract: OBJECTIVE
  The aim of this study was to investigate the physicochemical stability of clofarabine (CAFdA) injection concentrate and ready-to-use CAFdA infusion solutions over a prolonged period of 28 days.
  
  
  METHODS
  To determine the stability of CAFdA infusion solutions, the injection concentrate (Evoltra®, 1 mg/mL, Genzyme) was diluted either with 0.9% sodium chloride or 5% glucose infusion solution. The resulting concentrations of 0.2 mg/mL or 0.6 mg/mL, respectively, were chosen to represent the lower and upper limit of the ordinary concentration range. Test solutions were stored under refrigeration (2-8°C) or at room temperature either light protected or exposed to light. CAFdA concentrations and pH values were determined at different time intervals throughout a 28-day storage period. Compatibility of diluted CAFdA infusion solutions (0.1-0.4 mg/mL) with different container materials (polyvinyl chloride (PVC), glass, and polypropylene/polyethylene (PP/PE)) was tested over a 48-h storage period. CAFdA concentrations were measured by a stability-indicating reversed phase high-performance liquid chromatography (HPLC) assay with ultraviolet detection.
  
  
  RESULTS
  CAFdA injection concentrate and CAFdA infusion solutions remained physicochemically stable (>90% CAFdA) for 4 weeks. Results are independent of storage conditions, drug concentrations (0.2, 0.6, and 1.0 mg/mL) and diluents (0.9% sodium chloride, 5% glucose infusion solution). Adsorption of CAFdA to container material can be excluded.
  
  
  CONCLUSIONS
  CAFdA injection concentrate and diluted infusion solutions in commonly used vehicles are stable for at least 28 days either refrigerated or at room temperature. Physicochemical stability favors pharmacy-based centralized preparation. Due to microbiological reasons, strict aseptic handling and storage of the products under refrigeration is recommended.
authors.affiliation: Department of Pharmacy, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Kaiser
authors.forename: Irene
authors.initials: I
authors.lastname: Krämer
mesh_terms: D000227:Adenine Nucleotides / Q000032:analysis* / Q000737:chemistry* / Q000592:standards; D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry* / Q000592:standards; D001087:Arabinonucleosides / Q000032:analysis* / Q000737:chemistry* / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D000077866:Clofarabine; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods / Q000592:standards; D007262:Infusions, Intravenous / Q000592:standards; D019999:Pharmaceutical Solutions / Q000032:analysis / Q000737:chemistry / Q000592:standards; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D019999:Pharmaceutical Solutions; D000077866:Clofarabine