Conditions causing gemcitabine crystallization.
Susan Manners1, Peter Galettis, Paul de Souza
1Cancer Pharmacology and Therapeutics Laboratory, St. George Hospital Clinical School, University of New South Wales, Kogarah, New South Wales, Australia.
Summary
Alkaline adjusted gemcitabine (chemotherapy) can crystallize in syringes when stored cold, reducing drug concentration. This crystallization is reversible by returning samples to room temperature.
Area of Science:
- Oncology
- Pharmaceutical Chemistry
Background:
- Intravesical chemotherapy is standard for superficial bladder cancer.
- Alkaline-adjusted gemcitabine was used in a phase II study.
- Crystallization issues arose with pre-prepared gemcitabine syringes.
Purpose of the Study:
- Investigate conditions causing gemcitabine crystallization.
- Determine factors affecting gemcitabine stability in solution.
Main Methods:
- Gemcitabine solutions prepared in syringes under varied pH, temperature, and duration.
- Samples analyzed for crystallization up to 48 hours.
- High-performance liquid chromatography used to quantify gemcitabine concentration.
Main Results:
- Bicarbonate treatment and low temperatures promoted gemcitabine crystallization.
- Crystallization reduced gemcitabine concentration in pre-prepared syringes.
- Crystallization was reversible upon warming to room temperature.
Conclusions:
- Gemcitabine solutions may crystallize when pH is raised with sodium bicarbonate and stored cold.
- Careful control of pH and storage temperature is crucial for intravesical gemcitabine.
- Understanding stability prevents reduced drug efficacy in bladder cancer treatment.
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