The Degradation of Mitomycin C Under Various Storage Methods

Kinast, Robert; Akula, Kiran Kumar; DeBarber, Andrea E.; Barker, Gordon T.; Gardiner, Stuart K.; Whitson, Emily; Mansberger, Steven L.

doi:10.1097/ijg.0000000000000287

Cited by 11 publications

(11 citation statements)

References 12 publications

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“…Degradants, not believed to be cytotoxic, appeared in trace quantities following a 24 h storage period at room temperature of MMC 0.4 mg/mL solutions prepared in sterile water [19]. MMC degradation is accelerated under strong acidic and alkaline conditions [36, 37], which were not present in the tested samples (pH approximately 7.0).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, MMC infusion solutions of 1.0 mg/mL prepared in phosphate-buffered saline were stable when stored at room temperature for at least 7 days, but rapidly precipitated under refrigeration [18]. Kinast et al recently assessed the chemical stability of MMC 0.4 mg/mL solutions prepared in sterile water for ophthalmic delivery while stored under various cooling conditions [19]. After warming to room temperature, all solutions were chemically stable for at least 24 h [19].…”

Section: Introductionmentioning

confidence: 99%

“…Kinast et al recently assessed the chemical stability of MMC 0.4 mg/mL solutions prepared in sterile water for ophthalmic delivery while stored under various cooling conditions [19]. After warming to room temperature, all solutions were chemically stable for at least 24 h [19]. …”

Section: Introductionmentioning

confidence: 99%

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Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration

et al. 2017

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BackgroundMitomycin C (MMC) is an antitumor agent that is often administered intravesically to treat bladder cancer. Pharmacologically optimized studies have suggested varying methods to optimize delivery, with drug concentration and solution volume being the main drivers. However, these MMC concentrations (e.g. 2.0 mg/mL) supersede its solubility threshold, raising major concerns of inferior drug delivery.ObjectiveIn this study, we seek to confirm that the pharmacologically optimized MMC concentrations are achievable in clinical practice through careful modifications of the solution preparation methods.MethodsMMC admixtures (1.0 and 2.0 mg/mL) were prepared in normal saline using conventional and alternative compounding methods. Conventional methodology resulted in poorly soluble solutions, with many visible particulates and crystallates. However, special compounding methods, which included incubation of solutions at 50 °C for 50 min followed by storage at 37 °C, were sufficient to solubilize drug. Chemical degradation of MMC solutions was determined over 6 h using high-performance liquid chromatography (HPLC) analytics, while physical stability was tested in parallel.ResultsImmediately following the 50 min incubation, both MMC solutions exhibited approximately 5–7% drug degradation. Based on the measured concentrations and linear regression of degradation plots, additional storage of these solutions at 37 °C for 5 h retained chemical stability criterion (< 10% overall drug loss). No physical changes were observed in any solutions at any test time points.ConclusionWe recommend that the described alternative preparation methods may improve intravesicular delivery of MMC in this urological setting, and advise that clinicians employing these changes should closely monitor patients for MMC toxicities and pharmacodynamics (change in clinical outcomes) that result from the potential enhancement of MMC exposure in the bladder.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration

et al. 2017

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“…However, previous papers [5,12] have already postulated a rapid MMC degradation at 0.4 mg/mL over the time at room temperature. At 0.05 mg/mL MMC was not stable over 12 h in room temperature condition or in cold condition (5°C) [13].…”

Section: Analysis Timementioning

confidence: 99%

Stability of Reconstituted and Diluted Mitomycin C Solutions in Polypropylene Syringes and Glass Vials

Briot

Truffaut

Quay

et al. 2016

Pharmaceutical Technology in Hospital Pharmacy

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Abstract: Mitomycin C (MMC) is widely used in treatment of non-muscle invasive bladder cancer at a 1 mg/mL concentration, by intravesical instillation. MMC is also used as an ophthalmic procedure in glaucoma care mostly with 0.2 mg/mL concentration. To accelerate syringes provision, it could be interesting to demonstrate the stability of the drug, in order to be able to prepare the chemotherapeutic drug several hours before the chemotherapy administration.: A stability indicating HPLC-UV method was developed and validated according to the ICH guidelines. Concentrations of the MMC stored at 25 °C and 60 % of relative humidity and protected from light in polypropylene syringes (1 mg/mL and 0.2 mg/mL) or glass vials (1 mg/mL) were evaluated for 96 h and compared to the initial observed concentrations.: MMC stability was demonstrated in syringes and glass vials at 1 mg/mL only for 8 h in water for injections and for 10 h at 0.2 mg/mL in 0.9 % sodium chloride solutions, because relative concentrations (95 % confidence interval of the mean of 3 samples) were systematically over 90 % of the initial concentrations. After 96 h the relative concentrations were found below 80 % as compared to initial concentrations, thus indicating instability of these solutions. Degradation products were observed and remained below 3 %.: This study confirms that MMC solutions for ophthalmic application at 0.2 mg/mL or vesical instillation at 1 mg/mL have to be formulated extemporaneously to maintain the desired concentration.

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“…Due to their low stability in solution, different methods for both thiotepa and mitomycin C were used in degradation studies 140,200 or in stability studies of pharmaceutical formulations. [201][202][203][204]205 These methods were mainly based on LC-UV. Since thiotepa metabolism is still uncertain, LC-MS methods were also developed more recently for the identification of potential metabolites.…”

Section: Dna Interactive Agentsmentioning

confidence: 99%

Antineoplastic drugs and their analysis: a state of the art review

Guichard

Guillarme

Bonnabry

et al. 2017

Analyst

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The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

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The Degradation of Mitomycin C Under Various Storage Methods

Abstract: 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.

Cited by 11 publications

References 12 publications

Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration

Solubilization and Stability of Mitomycin C Solutions Prepared for Intravesical Administration

Stability of Reconstituted and Diluted Mitomycin C Solutions in Polypropylene Syringes and Glass Vials

Antineoplastic drugs and their analysis: a state of the art review

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