Idarubicin, a semi-synthetic anthracycline, is widely used in treatment regimens for acute myeloblastic and lymphoblastic leukemias in children and adults. For intravenous administration in hematology, idarubicin is commonly diluted in infusion bags with 0.9% sodium chloride (NaCl) or 5% dextrose (Dex). Routine clinical practice in high-volume centers can require preparing multiple idarubicin bags in advance for logistical reasons, so hospital pharmacists need reliable stability data that reflect current preparation methods and recommended stability-study procedures.
Previous published stability information for idarubicin diluted in solvents is limited. The main prior study assessed a single concentration in polypropylene tubes at room temperature and lacked detailed physicochemical endpoints now recommended for stability studies. Extrapolating older data to different concentrations, container types, solvents or storage temperatures poses risks for pharmacists producing these sterile cytotoxic preparations. This study was designed to evaluate the physicochemical stability of idarubicin diluted in polyolefin-type infusion bags (Freeflex + ®) at concentrations and storage conditions aligned with routine hematology practice.
Commercial Zavedos® idarubicin (10 mg/10 mL) was used to prepare 100 mL infusion bags. Polyolefin Freeflex + ® bags were selected as the container, with the primary internal film made of polypropylene and the secondary external film a polypropylene/polyethylene admixture. All preparations were produced under aseptic conditions in an ISO 5 negative-pressure isolator and stored protected from UV in photoprotective secondary packaging.
Protective measures for personnel and product handling were applied throughout sample preparation and quality control, including work within controlled-atmosphere areas, use of appropriate personal protective equipment, and handling under class II biological safety cabinets where required.
A preliminary analysis of University Hospital of Bordeaux production records (2016–2023) guided concentration selection. Over that period, 2,172 idarubicin bags were prepared for adult and pediatric oncohematology care. Production spanned 23 different concentrations between 0.02 and 0.28 mg/mL; about 87% of preparations centered between 0.09 and 0.15 mg/mL. To cover routine variability while focusing on the most common ranges, the study evaluated two concentrations: 0.04 mg/mL and 0.2 mg/mL, which bracket typical clinical values and include extremes used less frequently.
Three factors were tested in a fully crossed design: diluent (0.9% NaCl or 5% Dex), final concentration (0.04 mg/mL or 0.2 mg/mL) and storage temperature (refrigerated 5 ± 3 °C or room temperature 22 ± 3 °C). This yielded eight distinct conditions. For each condition, three bags were prepared (triplicates), totaling 24 bags. Samples were assayed on a scheduled series of days to track stability over one month.
Chemical stability was assessed using a validated, stability-indicating high-performance liquid chromatography method coupled to an ultraviolet/visible diode array detector (HPLC-UV/VIS DAD). The HPLC method was adapted from published methodology and performed on a Thermo Scientific UltiMate 3000 system with a photodiode array detector. Assays occurred on days D0, D1, D2, D7, D15, D22 and D30. The analytical approach aimed to quantify idarubicin concentration over time and to detect any degradation products.
Physical stability evaluations were performed on days D0, D15 and D30. These included visual inspection for color change or precipitation, sub-visible particle counting to assess particulate load against recommended limits, and measurement of pH and osmolality to detect any physicochemical shifts during storage.
Across all tested conditions (both diluents, both concentrations and both storage temperatures), measured idarubicin concentrations remained above 95% of the initial concentration throughout the 30-day study period. The stability-indicating HPLC-UV/VIS DAD assay did not detect degradation products under the study conditions.
No visible color change or precipitation was observed by naked-eye inspection at any evaluated timepoint. Sub-visible particle counts remained below recommended limits for the tested preparations. Recorded pH and osmolality values showed no change from baseline (D0) at the assessed timepoints.
This study demonstrates that idarubicin diluted to concentrations between 0.04 and 0.2 mg/mL in 0.9% NaCl or 5% dextrose and stored in polyolefin Freeflex + ® bags is chemically and physically stable for up to 30 days when protected from UV at either refrigerated (5 ± 3 °C) or room temperature (22 ± 3 °C). These findings extend prior limited data by testing clinically relevant concentration ranges, using infusion bags representative of routine practice rather than polypropylene tubes, and including contemporary physicochemical endpoints (visible/sub-visible particles, pH, osmolality) together with a stability-indicating HPLC assay.
For hospital pharmacies and hematology treatment centers that prepare multiple idarubicin infusions in advance, these results provide evidence to support extended in-use periods under the precise conditions studied. Pharmacists should note that the conclusions apply only to the tested combinations of concentration, diluent, container type, storage temperature and protection from UV as described in the study.
Under the reported experimental conditions, idarubicin preparations made from Zavedos® and diluted in Freeflex + ® polyolefin infusion bags to concentrations between 0.04 and 0.2 mg/mL in either 0.9% NaCl or 5% dextrose remained chemically and physically stable for 30 days at 5 ± 3 °C or 22 ± 3 °C when protected from UV. The stability-indicating HPLC-UV/VIS DAD assay showed concentrations above 95% of initial values and no detectable degradation products, with no adverse changes in particles, pH or osmolality.