A Novel Capillary Electrophoresis Capacitively Coupled Contactless Conductivity Detection (CE‑C⁴D) Method for Quantification of Ionic Excipients in Doxorubicin HCl Liposome Injection.

Authors

Savithra Jayaraj, Prabhath Gamage, Wenlei Jiang, Thilak Mudalige

Published in

ACS omega. Volume 11. Issue 26. Pages 39124-39133. Jul 07, 2026. Epub Jun 22, 2026.

Abstract

Pegylated liposomal doxorubicin (DOX) was recognized for its efficient drug delivery, reduced toxicity, and prolonged circulation. Ammonium sulfate ((NH₄)₂SO₄) plays a critical role in DOX loading and retention within liposomes, and intraliposomal (NH₄)₂SO₄ concentrations above 200 mM are essential for stable DOX sulfate nanocrystal generation and liposomal stability. Currently available methods, such as ion chromatography, for the selective quantitation of liposomal encapsulated ions require time-consuming separation steps. In this study, a capillary electrophoresis-based separation method coupled with capacitively coupled contactless conductivity detection (CE-C⁴D) was developed and validated for the direct quantitation of total (internal + external) and external ionic excipients in DOX liposomal formulations. Cation and anion analyses, conducted under positive and negative polarities, respectively, demonstrated distinct migration orders (NH₄ ⁺, K⁺, Na⁺, Li⁺ for cations; Cl^-, SO₄ ^2-, F^- for anions) with excellent baseline separation and peak resolution. The method demonstrates linearity with correlation coefficients consistently above 0.999 and low limits of quantitation (below 8.22 μM) for all analyzed ions. The optimized CE-C⁴D method allowed accurate quantitation of total and external ion concentrations including NH₄ ⁺, K⁺, Na⁺, Cl^-, and SO₄ ^2- ions in liposomal DOX formulations. All tested liposomal DOX formulations contained an excess of 200 mM (NH₄)₂SO₄ within liposomes. This method provides an alternative for accurate quantitation of ion species present in liposomal formulations, supporting both brand and generic liposome formulation development and regulatory assessment.

PMID:
42428904
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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