One-month physicochemical stability study of idarubicin prepared in polyolefin-type bags for the treatment of hematological diseases
Guillaume Bouguéon, Arthur Jouvien, Jean-Marc Bernadou, Arnaud Venet, Aude Berroneau, Pierre Mora, Fabien Xuereb
Abstract
Idarubicine is a mainstay of the treatment strategy for hematological cancer. The literature lacks stability data that comply with current preparation practices and recommendations for conducting stability studies. The aim of the present work is to establish the stability of idarubicin preparations diluted in polyolefin-type bags (Freeflex + ®) for intravenous administration in hematological clinical settings. Preparations were produced by diluting Zavedos® idarubicin in Freeflex + ® bags containing 0.9% sodium chloride (NaCl) or 5% dextrose (Dex) at concentrations of 0.04 mg/mL and 0.2 mg/mL.
Introduction
Idarubicin, a semi-synthetic anthracycline (S1 Fig), remains a mainstay of the treatment strategy for newly-diagnosed acute myeloblastic leukemia in children and adults, or for patients with relapsed or refractory disease, ahead of other anthracyclines. Idarubicin is also used in the treatment of recurrent acute lymphoblastic leukemia in children and adults [1–3]. For solid tumors, idarubicin is used in gastroenterology in transarterial chemoembolization (TACE) therapies mixed with contrast medium emulsions (e.g., Lipiodol®) for the treatment of intermediate-stage liver carcinoma [4].
Materials and method
Materials
Idarubicin 10 mg/10 mL (Zavedos®, Pfizer, New York City, NY, US) (batches CA7906 exp: 2022 03 and DX0725 exp: 2023 03) was used to prepare idarubicin bags of 100 mL 0.9% sodium chloride (NaCl) and 100 mL 5% dextrose (Dex). For solution dilution, Freeflex + ® bags were purchased from Fresenius Kabi (Bad Homburg vor der Höhe, Germany). The infusion bags were made of polyolefin (primary internal film: polypropylene; secondary external film: polypropylene/polyethylene admixture).
Results
Assay method validation
The chromatograms obtained showed a well-defined and symmetrical peak with a mean retention time of 3.4 min and baseline only exhibiting a low level of background noise (Fig 1). The calibration curves produced on 3 different days, were linear with a correlation coefficient (R2) of 0.999. Both the intraday and interday repeatability have produced satisfactory results (Table 1). The intraday and interday accuracies ranged between 98.09 and 101.73% and between 99.45 and 101.24% respectively.
Discussion
The present study focused on the brand-name drug Zavedos®, the most important idarubicin presentation on the market, in ready-to-use form, in which the excipients are glycerol, hydrochloric acid (QS pH from 3 to 4) and water for injections. It was conducted on Freeflex + ® infusion bags made of polyolefins.
Conclusion
The present study provides robust data on the stability of idarubicin preparations administered in bags for hematology indications, and complies with current requirements in terms of stability studies. It updates the data available to date and demonstrates that idarubicin preparations are chemically and physically stable for up to 30 days at low (0.04 mg/mL) and high (0.2 mg/mL) concentrations in 0.9% NaCl and 5% Dex polyolefin-type bags (Freeflex + ®) for infusion, protected from UV, with no effect of temperature during storage (refrigeration 5 ± 3 °C and room temperature 22 ± 3 °C). This will enable hospital pharmacies to prepare medicines safely, optimise advanced preparation processes, and will also provide data in the event of non-compliance with storage conditions.
Citation: Bouguéon G, Jouvien A, Bernadou J-M, Venet A, Berroneau A, Mora P, et al. (2026) One-month physicochemical stability study of idarubicin prepared in polyolefin-type bags for the treatment of hematological diseases. PLoS One 21(8): e0356906. https://doi.org/10.1371/journal.pone.0356906
Editor: Christophe Curti, Assistance Publique - Hôpitaux de Marseille, FRANCE
Received: February 17, 2026; Accepted: August 10, 2026; Published: August 28, 2026
Copyright: © 2026 Bouguéon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: No authors have competing interests.
