title: Conditions causing gemcitabine crystallization.
abstract: BACKGROUND
  Intravesical delivery of chemotherapy agents is used very commonly for the treatment of superficial bladder cancer. We recently completed a phase II study of intravesical gemcitabine in which an alkaline adjusted gemcitabine preparation was used initially, based on very early phase I studies. However, crystallization was noted in some of the pre-prepared syringes, which prompted us to investigate the conditions under which gemcitabine crystallized.
  
  
  METHODS
  Gemcitabine was prepared in syringes in triplicate and conditions were varied with respect to pH, temperature, and duration. Samples were observed for up to 48 h for the development of crystallization. High-performance liquid chromatography analysis of gemcitabine concentrations was undertaken for all samples.
  
  
  RESULTS
  Crystallization of gemcitabine was favored under conditions of bicarbonate treatment and lowering of temperature. However, the process was reversible, as demonstrated by recovery of gemcitabine concentrations in samples brought back to room temperature. Crystallization resulted in reduction of gemcitabine concentrations in the pre-prepared syringes.
  
  
  CONCLUSIONS
  Gemcitabine solutions may be associated with crystallization if the native pH is increased with the addition of sodium bicarbonate, and samples are stored in a cold environment.
authors.affiliation: Cancer Pharmacology and Therapeutics Laboratory, St. George Hospital Clinical School, University of New South Wales, Kogarah, New South Wales, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Manners
authors.forename: Peter
authors.initials: P
authors.lastname: Galettis
authors.forename: Paul de
authors.initials: Pd
authors.lastname: Souza
mesh_terms: D000283:Administration, Intravesical; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003080:Cold Temperature / Q000009:adverse effects*; D003460:Crystallization; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004356:Drug Storage / Q000379:methods / Q000592:standards*; D006863:Hydrogen-Ion Concentration; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000093542:Gemcitabine