Microbial inhibitory properties and stability of topotecan hydrochloride injection

The viability of five microorganisms in topotecan 1 mg/mL (as the hydrochloride salt) in sterile water and the stability of the drug were studied. Duplicate portions of topotecan 1 mg/mL were inoculated with Escherichia coli. The process was repeated for Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Samples were removed from each solution initially and after 6, 16, and 24 hours and 3, 7, 14, 21, and 28 days of incubation at 20-25 degrees C. To test stability, vials of reconstituted topotecan hydrochloride injection were stored at each of three temperatures--5, 25, and 30 degrees C--and other vials were used for time zero analysis. For each temperature, vials were removed at 1, 7, and 14 days and the remaining vials at 28 days for analysis by high-performance liquid chromatography and for visual and pH assessment. P. aeruginosa, S. aureus, and E. coli lost viability at 16 hours, 24 hours, and 28 days, respectively. C. albicans and A. niger did not lose viability, but their numbers did not grow. No differences in color or clarity were observed, and pH was constant. In all solutions, the topotecan concentration was > 98% of the initial concentration. Topotecan 1 mg/mL in sterile water stored at 20-25 degrees C for up t 28 days did not support growth of the five microorganisms studied; in solutions stored at 5, 25, or 30 degrees C for up to 28 days, topotecan 1 mg/mL remained stable.