{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:06:22Z","timestamp":1789103182084,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Etilefrine is a sympathomimetic agent increasingly used off-label as a rescue therapy for refractory neonatal chylothorax. For continuous intravenous administration in neonates, the commercially available 10 mg\/mL formulation requires substantial dilution to a concentration of 4 \u00b5g\/mL. However, stability data for these highly diluted preparations are currently lacking. Hence, this study aimed to assess the short-term physicochemical stability of etilefrine diluted to 4 \u00b5g\/mL in 0.9% sodium chloride or 5% dextrose. Methods: Etilefrine was quantified using a high-performance liquid chromatography method coupled with ultraviolet detection. Diluted solutions were prepared in 10 mL polypropylene syringes, maintained at room temperature, and analyzed daily for 96 h. Physicochemical stability assessment included visual inspection for physical changes, assays of drug concentration, pH, osmolality, and subvisible particle counts. Results: Throughout the 96 h, no visible changes, such as precipitation, discoloration, or haze, were observed. Etilefrine concentrations in both isotonic diluents remained within 10% of the initial value. There were no significant variations in pH and osmolality. Subvisible particle counts remained below the limits established by the European Pharmacopoeia. Conclusions: Etilefrine diluted to 4 \u00b5g\/mL in 0.9% sodium chloride or 5% dextrose in syringes remained physicochemically stable for 96 h at room temperature. These findings provide practical stability data to support the preparation and administration of diluted etilefrine, and may facilitate the standardization of its use in future clinical studies of refractory neonatal chylothorax.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091135","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:01:56Z","timestamp":1788966116000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diluted Etilefrine for Neonatal Chylothorax: A 96-Hour Physicochemical Stability Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-6171","authenticated-orcid":false,"given":"Louisa","family":"Bourel","sequence":"first","affiliation":[{"name":"CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associ\u00e9es, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixtine","family":"Gilliot","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associ\u00e9es, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"Boulos","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associ\u00e9es, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousra","family":"Alouadni","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associ\u00e9es, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4970-4458","authenticated-orcid":false,"given":"K\u00e9vin","family":"Le Duc","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 2694 METRICS: Evaluation des Technologies de Sant\u00e9 et des Pratiques M\u00e9dicales-Perinatal Environment and Health, University Lille, F-59000 Lille, France"},{"name":"CHU Lille, Department of Neonatology, Jeanne de Flandre Hospital, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Riadh","family":"Boukhris","sequence":"additional","affiliation":[{"name":"CHU Lille, Department of Neonatology, Jeanne de Flandre Hospital, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Storme","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 2694 METRICS: Evaluation des Technologies de Sant\u00e9 et des Pratiques M\u00e9dicales-Perinatal Environment and Health, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0089-5284","authenticated-orcid":false,"given":"Anthony","family":"Martin Mena","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associ\u00e9es, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Odou","sequence":"additional","affiliation":[{"name":"CHU Lille, ULR 7365-GRITA-Groupe de Recherche sur les Formes Injectables et les Technologies Associ\u00e9es, University Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","first-page":"75","article-title":"Dynamics of Pleural Fluid Effusion and Chylothorax in the Fetus and Newborn: Role of the Lymphatic System","volume":"46","author":"Bellini","year":"2013","journal-title":"Lymphology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.21037\/jtd-23-1636","article-title":"Chylothorax: Pathophysiology, Diagnosis, and Management\u2014A Comprehensive Review","volume":"16","author":"Bhatnagar","year":"2024","journal-title":"J. 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