title: Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.
abstract: OBJECTIVE
  Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real-time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery. Extemporaneous preparation of proflavine solution for these diagnostic procedures requires preparation in batches and long-term storage to improve compounding efficiency in the pharmacy. However, there is a paucity of long-term stability data for proflavine contrast solutions.
  
  
  METHODS
  The physical and chemical stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in sterile water was determined following storage at refrigeration (4-8℃) and room temperature (23℃). Concentrations of proflavine were measured at predetermined time points up to 12 months using a validated stability-indicating high-performance liquid chromatography method.
  
  
  RESULTS
  Proflavine solutions stored under refrigeration were physically and chemically stable for at least 12 months with concentrations ranging from 95% to 105% compared to initial concentration. However, in solutions stored at room temperature increased turbidity and particulates were observed in some of the tested vials at 9 months and 12 months with peak particle count reaching 17-fold increase compared to baseline. Solutions stored at room temperature were chemically stable up to six months (94-105%).
  
  
  CONCLUSIONS
  Proflavine solutions at concentration of 0.01% were chemically and physically stable for at least 12 months under refrigeration. The solution was chemically stable for six months when stored at room temperature. We recommend long-term storage of proflavine solutions under refrigeration prior to diagnostic procedure.
authors.affiliation: Department of Pharmacy Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA jdkawedia@mdanderson.org.
authors.forename: Jitesh D
authors.initials: JD
authors.lastname: Kawedia
authors.affiliation: Department of Pharmacy Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Myers
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Richards-Kortum
authors.affiliation: Department of Pharmacy Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kramer
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Gillenwater
authors.affiliation: Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kirk S
authors.initials: KS
authors.lastname: Culotta
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D009062:Mouth Neoplasms / Q000188:drug therapy; D019999:Pharmaceutical Solutions / Q000737:chemistry* / Q000627:therapeutic use; D011370:Proflavine / Q000737:chemistry* / Q000627:therapeutic use; D012034:Refrigeration / Q000379:methods
chemical_list: D003287:Contrast Media; D019999:Pharmaceutical Solutions; D011370:Proflavine
keywords: Proflavine; chemical stability; contrast agent; oral cancer; physical stability