title: Concentration Accuracy of Compounded Mitomycin C for Ophthalmic Surgery.
abstract: OBJECTIVE
  Ophthalmologists rely on accurate concentrations of mitomycin C (MMC) to prevent scarring with trabeculectomy surgery. To our knowledge, the concentration accuracy and variability of compounded MMC are unknown.
  
  
  OBJECTIVE
  To determine whether the measured concentration differs from the expected concentration of 0.4 mg/mL of MMC used in ophthalmic surgery.
  
  
  METHODS
  Laboratory experimental investigation conducted in July 2013. We acquired 60 samples of 0.4 mg/mL of MMC from a spectrum of common compounding and storage techniques (refrigeration, freezing, and immediately compounded dry powder) and a variety of pharmacies (an academic hospital, a community hospital, and an independent Pharmacy Compounding Accreditation Board-accredited pharmacy). We used C18 reversed-phase high-performance liquid chromatography to measure the MMC concentration of all samples. We used pure MMC (Medisca Inc) to generate calibration curves and sulfanilamide as an internal standard.
  
  
  METHODS
  We calculated MMC concentration using a calibration curve (range, 0.3-0.5 mg/mL) generated by dividing MMC peak area by internal standard peak area and plotting the area ratio against the calibrant concentrations. We compared the measured concentration against the expected 0.4 mg/mL concentration for all samples.
  
  
  RESULTS
  Measurement of MMC using the high-performance liquid chromatography method demonstrated acceptable accuracy (92%-100%), precision (2%-6% coefficient of variation), and linearity (mean correlation coefficient of r2 = 0.99). The measured MMC concentration determined using the high-performance liquid chromatography method for all samples was 12.5% lower than the expected 0.4 mg/mL value (mean [SD], 0.35 [0.04] mg/mL; 95% CI, 0.34-0.36; P < .001) with a wide concentration range between 0.26 and 0.46 mg/mL.
  
  
  CONCLUSIONS
  Common compounding and storage techniques for MMC resulted in a lower accuracy and wider range of concentration than expected. These differences in concentration may result from compounding techniques and/or MMC degradation. Variability in MMC concentration could cause inconsistency in glaucoma surgical results, but the clinical relevance of such findings on glaucoma surgery outcomes remains unknown.
authors.affiliation: Devers Eye Institute, Legacy Health, Portland, Oregon.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kinast
authors.affiliation: RS Dow Neurobiology Laboratories, Legacy Research Institute, Portland, Oregon.
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Akula
authors.affiliation: Devers Eye Institute, Legacy Health, Portland, Oregon.
authors.forename: Steve L
authors.initials: SL
authors.lastname: Mansberger
authors.affiliation: Devers Eye Institute, Legacy Health, Portland, Oregon.
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Barker
authors.affiliation: Devers Eye Institute, Legacy Health, Portland, Oregon.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Gardiner
authors.affiliation: Devers Eye Institute, Legacy Health, Portland, Oregon.
authors.forename: Emily
authors.initials: E
authors.lastname: Whitson
authors.affiliation: Oregon Health and Science University, Portland.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: DeBarber
mesh_terms: D000477:Alkylating Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000592:standards*; D004356:Drug Storage; D005355:Fibrosis / Q000517:prevention & control; D005901:Glaucoma / Q000601:surgery; D006801:Humans; D016685:Mitomycin / Q000032:analysis*; D009883:Ophthalmic Solutions / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D014130:Trabeculectomy
chemical_list: D000477:Alkylating Agents; D009883:Ophthalmic Solutions; D004364:Pharmaceutical Preparations; D016685:Mitomycin