The Degradation of Mitomycin C Under Various Storage Methods.

Abstract

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