title: Rapid loss of fentanyl citrate admixed with fluorouracil in polyvinyl chloride containers.
abstract: OBJECTIVE
  To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 micrograms/mL in dextrose 5% and in sodium chloride 0.9% injection.
  
  
  METHODS
  Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at -20, 4, 23, and 32 degrees C. Samples were removed immediately and at various times over 7 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC.
  
  
  RESULTS
  Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23, 32 degrees C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0-9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time.
  
  
  CONCLUSIONS
  When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 micrograms/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.
authors.affiliation: Division of Pharmacy, University of Texas, MD Anderson Cancer Center, Houston, USA.
authors.forename: Q A
authors.initials: QA
authors.lastname: Xu
authors.forename: L A
authors.initials: LA
authors.lastname: Trissel
authors.forename: J F
authors.initials: JF
authors.lastname: Martinez
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D004338:Drug Combinations; D004344:Drug Incompatibility; D004349:Drug Packaging; D004355:Drug Stability; D005283:Fentanyl / Q000737:chemistry*; D005472:Fluorouracil / Q000737:chemistry*; D005947:Glucose; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry*; D007275:Injections, Intravenous; D011143:Polyvinyl Chloride / Q000737:chemistry*; D012965:Sodium Chloride
chemical_list: D000701:Analgesics, Opioid; D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D007166:Immunosuppressive Agents; D012965:Sodium Chloride; D011143:Polyvinyl Chloride; D005947:Glucose; D005472:Fluorouracil; D005283:Fentanyl