MICROBIAL INHIBITORY PROPERTIES AND STABILITY OF TOPOTECAN HYDROCHLORIDE INJECTION

The viability of five microorganisms in topotecan 1 mg/mL (as the hydr ochloride salt) in sterile water and the stability of the drug were st udied. Duplicate portions of topotecan 1 mg/mL were inoculated with Es cherichia coli. The process was repeated for Pseudomonas aeruginosa, S taphylococcus aureus, Candida albicans, and Aspergillus niger. Samples were removed from each solution initially and after 6, 16, and 24 hou rs and 3, 7, 14, 21, and 28 days of incubation at 20-25 degrees C. To test stability, vials of reconstituted topotecan hydrochloride injecti on were stored at each of three temperatures-5, 25, and 30 degrees C-a nd 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 v isual and pH assessment. P. aeruginosa, S. aureus, and E. coli lost vi ability at 16 hours, 24 hours, and 28 days, respectively. C. albicans and A. niger did not lose viability, but their numbers did not grow. N o differences in color or clarity were observed, and PPI 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 deg rees C for up to 28 days did not support growth of the five microorgan isms studied; in solutions stored at 5, 25, or 30 degrees C for up to 28 days, topotecan 1 mg/mL remained stable.