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The Degradation of Mitomycin C Under Various Storage Methods

Kinast, Robert M. MD; Akula, Kiran K. PhD; DeBarber, Andrea E. PhD; Barker, Gordon T. MS; Gardiner, Stuart K. PhD; Whitson, Emily; Mansberger, Steve L. MD, MPH

doi: 10.1097/IJG.0000000000000287
Original Studies

Purpose: To compare the effects of common pharmacy preparation and storage conditions on the stability of mitomycin C (MMC) in solution.

Methods: We used C18 reversed-phase high-performance liquid chromatography to determine the stability of 0.4 mg/mL MMC solutions, and liquid chromatography-electrospray ionization-mass spectrometry to identify degradation products. Conditions compared were: compounding and storage by refrigeration (1 and 2 wk), freezing (23 d), shipment “on-ice” (1 mo frozen followed by 1-wk refrigeration), and immediately compounding dry powder (Mitosol; Mobius Therapeutics LLC). We tested 3 samples for each storage method when samples reached room temperature (time 0), and then 1, 4, and 24 hours later. We used MMC peak area as a percentage of total (MMC plus degradants) area detected with high-performance liquid chromatography as a measure of stability.

Results: We assessed MMC stability for 5 preparation and storage methods at 4 timepoints (with n=3 per timepoint). At time 0, we found similar stabilities for MMC (F=0.72, P=0.599) between all 5 storage methods: 1-week refrigerated (97.9±0.2%), dry powder (97.5±0.3%), 2-week refrigerated (96.9±0.2%), 23-day frozen (96.7±3.1%), and shipment on-ice (96.0±1.2%). However, MMC demonstrated significant degradation over a 24-hour period with 2-week refrigeration (95.7±0.3%, β=−0.1%/h, P<0.001) and shipment on-ice (93.1±1.8%, β=−0.1%/h, P=0.013). We identified small amounts (<3.2%) of 2 degradants, cis-hydroxymitosene and trans-hydroxymitosene, across all samples.

Conclusions: The different preparation and storage methods of MMC showed similar stability when used immediately upon reaching room temperature. However, degradation of MMC occurred with further storage at room temperature. The clinical implication of small amounts of MMC degradants is unclear.

*Devers Eye Institute at Legacy Health

RS Dow Neurobiology Laboratories, Legacy Research Institute

Oregon Health & Science University, Portland, OR

Presented at the American Glaucoma Society Annual Meeting, February 2014, Washington, DC.

Supported by unrestricted Research Grant from Mobius Therapeatics, LLC (St Louis, MO). Mobius Therapeutics LLC had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

R.M.K., K.K.A., A.E.D., G.T.B., S.K.G., E.W., S.L.M.: study concept and design. K.K.A., G.T.B., A.E.D., E.W.: acquisition of data. K.K.A., A.E.D., R.M.K.: analysis and interpretation of data. K.K.A., A.E.D., R.M.K., S.L.M.: drafting of manuscript. K.K.A., A.E.D., R.M.K., S.L.M.: critical revision of the manuscript for important intellectual content. G.T.B., S.K.G., R.M.K., S.L.M.: statistical analysis. R.M.K., S.L.M.: obtained funding. R.M.K., K.K.A., A.E.D., G.T.B., S.K.G., E.W., S.L.M.: administrative, technical, or material support.

R.M.K. and K.K.A. contributed equally.

Disclosures: R.M.K.: Research: Allergan, Mobius (relevant). S.L.M.: Consultant: Allergan, Envisia, Alcon, Santen, Welch-Allyn. Research: National Eye Institute, Allergan, Mobius (relevant). The remaining authors declare no conflict of interest.

Reprints: Robert M. Kinast, MD, Legacy Devers Eye Institute, 1040 NW 22nd Ave., Portland, OR 97210 (e-mail: rkinast@deverseye.org).

Received October 1, 2014

Accepted April 10, 2015

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