title: Stability of a highly concentrated solution of epirubicin for conventional transcatheter arterial chemoembolization.
abstract: BACKGROUND
  Epirubicin is widely used for conventional transcatheter arterial chemoembolization (cTACE) in patients with hepatocellular-carcinoma. However, there is no data about its stability in solution at concentration higher than 2 mg/L, yet needed when mixing it with a standard volume of Lipiodol(®) to produce an efficient water-in-oil emulsion. The aim of this study was therefore to evaluate the stability of a highly concentrated solution of epirubicin for cTACE and verify whether epirubicin solution could be prepared in advance.
  
  
  METHODS
  Fifty milligrams of epirubicin were dissolved in 6 mL of 0.9% sodium chloride and conditioned in brown polypropylene syringe. Physical and chemical stability assays including particles and HPLC-DAD analysis were performed in triplicate, using series of 5 syringes stored over 72 h at 4±2 °C followed by 4h at 22±4°C.
  
  
  RESULTS
  Neither weight loss nor pH or spectrum change occurred. No haze or turbidity was observed and the number of subvisible particles was below the recommended limits. Epirubicin concentration remained above 95% of the initial value over the 72 h of storage at +4 °C followed by 4h at 22±4 °C and no degradation was observed.
  
  
  CONCLUSIONS
  Epirubicin at 50mg/6 mL in 0.9% NaCl conditioned in brown propylene syringe is stable for at least 72 h at 4±2 °C with additional 4h at 22±4 °C allowing its preparation in advance for programmed cTACE and the standardization of its use in clinical practice.
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France; Department of Clinical Pharmacology, Amiens University Teaching Hospital, UPJV, INSERM U1088, Avenue Laennec, 80000 Amiens, France. Electronic address: bennis.youssef@chu-amiens.fr.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Bennis
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France. Electronic address: amandine.savry@ap-hm.fr.
authors.forename: Amandine
authors.initials: A
authors.lastname: Savry
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France. Electronic address: florian.correard@ap-hm.fr.
authors.forename: Florian
authors.initials: F
authors.lastname: Correard
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France. Electronic address: marc.montana@ap-hm.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Montana
authors.affiliation: Laboratory of Galenics, Biopharmaceutics and Pharmacy Cosmetology, Pharmaceutical Bioengineering Department, School of Pharmacy, AMU, 27 Boulevard Jean Moulin, 13005 Marseille, France. Electronic address: christophe.sauzet@univ-amu.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Sauzet
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France. Electronic address: laurence.Gauthier-villano@ap-hm.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Gauthier-Villano
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France. Electronic address: pascale.pisano@ap-hm.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Pisano
authors.affiliation: Oncopharma Unit, Pharmacy department, La Timone University Teaching Hospital, AP-HM, 264 rue St Pierre, 13005 Marseille, France. Electronic address: bertrand.pourroy@ap-hm.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pourroy
mesh_terms: D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D015251:Epirubicin / Q000737:chemistry*; D004998:Ethiodized Oil / Q000737:chemistry*; D012996:Solutions
chemical_list: D004655:Emulsions; D012996:Solutions; D015251:Epirubicin; D004998:Ethiodized Oil
keywords: Anthracycline; Cytotoxic drugs reconstitution; Hepatocellular-carcinoma; Interventional radiology; Transcatheter arterial chemoembolization