Stability of mitomycin in polypropylene syringes for use in glaucoma surgery

Abstract

Introduction: Outside the oncology field, mitomycin is used in glaucoma surgery. Solutions at 0.2 mg/mL are usually used to fully saturate sterile sponges that are applied to the treatment area. In hospital pharmacies, mitomycin 10 and 40 mg are classically used to prepare the solutions with a lot of losses. The objective of this work was to study the long-term stability to consider preparation in advance and reduce losses in a context of drug shortage. Methods: Two different products were used: Ametycine, which contains sodium chloride as excipient, and Mitomycin medac, which contains urea as excipient. Solutions at 0.1 mg/mL (sometimes used in our hospital) and the more classically used 0.2 mg/mL were prepared and stored in polypropylene syringes. Solutions were kept at −20°C or at 5°C and analyzed on day 28, 63, and 91. Chemical stability was studied by using a previously validated high-performance liquid chromatography stability-indicating method. pH was measured and a visual inspection was performed. Results: For each condition, solutions were not stable after long-term storage with concentrations below 90% of the initial concentration after 28 days. Frozen solutions were less stable than refrigerated solutions. pH values increased by more than 1 pH unit after 3 months. Ametycine shows precipitate after freezing but not solutions prepared with Mitomycin medac. The color of frozen solutions was changed from light blue to light green at −20°C but became light blue after thawing. Conclusion: Mitomycin 0.1 and 0.2 mg/mL showed an instability after long-term storage at 5°C or −20°C. These results do not allow the preparation in advance of large batches.

Physicochemical stability of ready-to-administer mitomycin C solutions for intravesical instillation

“…The HPLC method was adopted from Briot et al and proven as a stability indicating method 12 13. The absence of interference with urea was proven 13.…”

“…The HPLC method was adopted from Briot et al and proven as a stability indicating method 12 13. The absence of interference with urea was proven 13. The MMC parent peak and the peaks of degradation products were clearly separated.…”

“…A known reverse-phase high-performance liquid chromatography (RP-HPLC) method12 13 with photodiode array detection was used for quantitative analysis of MMC and degradation products. The HPLC system consisted of a Waters Alliance 2695 pump connected to a Waters Photodiode Array Detector 996 (Waters, Eschborn, Germany).…”

“…The mobile phase consisted of 65% 10 mM buffer solution (potassium dihydrogen phosphate; AppliChem, Darmstadt, Germany) dissolved in water HPLC grade (AppliChem) and 35% methanol HPLC grade (Fisher Scientific, Loughborough, UK). The flow rate was set to 1 mL/min, the detection wavelength to 216 nm (quantification of MMC)12 13 and 254 nm (detection of degradation products) 14. Run time was 10 min.…”

Low-dose erythromycin in pediatrics: Formulation and stability of 20 mg hard gelatin capsules

“…Disintegration tests were performed on 6 capsules at time zero, one month, 3 months, 8 months, and 12 months. Significant changes in erythromycin content were defined as a 10% change in dosage from its initial value as previously reported for hospital-compounded preparations [29][30][31][32][33].…”