title: Stability of tacrolimus solutions in polyolefin containers.
abstract: OBJECTIVE
  Results of a study to determine the stability of tacrolimus solutions stored in polyolefin containers under various temperature conditions are reported.
  
  
  METHODS
  Triplicate solutions of tacrolimus (0.001, 0.01, and 0.1 mg/mL) in 0.9% sodium chloride injection or 5% dextrose injection were prepared in polyolefin containers. Some samples were stored at room temperature (20-25 °C); others were refrigerated (2-8 °C) for 20 hours and then stored at room temperature for up to 28 hours. The solutions were analyzed by stability-indicating high-performance liquid chromatography (HPLC) assay at specified time points over 48 hours. Solution pH was measured and containers were visually inspected at each time point. Stability was defined as retention of at least 90% of the initial tacrolimus concentration.
  
  
  RESULTS
  All tested solutions retained over 90% of the initial tacrolimus concentration at all time points, with the exception of the 0.001-mg/mL solution prepared in 0.9% sodium chloride injection, which was deemed unstable beyond 24 hours. At all evaluated concentrations, mean solution pH values did not change significantly over 48 hours; no particle formation was detected.
  
  
  CONCLUSIONS
  During storage in polyolefin bags at room temperature, a 0.001-mg/mL solution of tacrolimus was stable for 24 hours when prepared in 0.9% sodium chloride injection and for at least 48 hours when prepared in 5% dextrose injection. Solutions of 0.01 and 0.1 mg/mL prepared in either diluent were stable for at least 48 hours, and the 0.01-mg/mL tacrolimus solution was also found to be stable throughout a sequential temperature protocol.
authors.affiliation: Pharmaceutical Development Section, Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, MD.
authors.forename: Jun H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, MD. bgoldspiel@nih.gov.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Goldspiel
authors.affiliation: Pharmaceutical Development Section, Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, MD.
authors.forename: Sujung
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Pharmaceutical Development Section, Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, MD.
authors.forename: Gopal K
authors.initials: GK
authors.lastname: Potti
mesh_terms: D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry*; D011090:Polyenes / Q000737:chemistry; D016559:Tacrolimus / Q000737:chemistry*
chemical_list: D007166:Immunosuppressive Agents; D011090:Polyenes; C035051:PL 732; D016559:Tacrolimus