Background and importance Newly formulated Thiotepa Riemser was approved in 2021 for conditioning treatment before allogeneic or autologous haematopoietic progenitor cell transplantation.
Prior to administration Thiotepa Riemser is reconstituted with water for injection and diluted with 0.9% sodium chloride or 5% glucose (G5) infusion solutions. According to the Summary of Product Characteristics, the ready-to-administer (RTA) infusion solutions are physicochemically stable for 24 hours stored at 2–8°C or 4 hours stored at room temperature. To our knowledge, long-term stability data have not yet been published. Of note, physicochemical stability improves when G5 infusion solutions are used as vehicle solutions.
Aim and objectives Due to lack of long-term stability data for newly formulated Thiotepa Riemser RTA solutions, the physicochemical in-use stability of diluted infusion solutions in prefilled G5 infusion bags was investigated.
Material and methods Thiotepa Riemser 1 mg/mL, 2 mg/mL and 3 mg/mL test solutions were prepared in triplicate using prefilled 5% glucose polyolefin bags. Test solutions were stored at 2–8°C or 25°C for 14 days. Directly after dilution and on days 1, 3, 5, 7, 14 the test solutions were inspected and samples withdrawn. Thiotepa concentrations were measured by a stability-indicating high-performance liquid chromatography (HPLC) method, adapted from the Thiotepa monographs in the British and US Pharmacopoeias. In parallel, pH and osmolality were measured. Non-visible particles were counted in the test solutions on days 0 and 14.
Results When Thiotepa Riemser test solutions were stored at 2–8°C, thiotepa concentrations remained above 98% of the initial concentration for 14 days. When stored at 25°C, thiotepa concentrations fell below 95% of the initial concentration after 3 days in 1 mg/mL solutions, 5 days in 2 mg/mL solutions and 7 days in 3 mg/mL solutions.
Peaks of unspecified impurities were detected in the chromatograms of all test solutions directly after dilution and degradation peaks increased during the storage time. Particle counts and osmolality remained unchanged in most test solutions. Values of pH increased slightly, especially when test solutions were stored at 25°C.
Conclusion and relevance Thiotepa Riemser infusion solutions diluted with G5 are physicochemically stable for 14 days when refrigerated and depending on the concentration for 3–7 days when stored at 25°C. Evaluation of the amount and relevance of unspecified impurities is ongoing.
Conflict of Interest Corporate sponsored research or other substantive relationships: research grant from Riemser Pharma GmbH Germany.