Determination of clodronate content in liposomal formulation by capillary zone electrophoresis

Pál Perjési, Taewook Kim, Alevtina D. Zharikova, Xiaoxu Li, Tennore Ramesh, Jeyanthi Ramasubbu, Laszlo Prokai

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Liposome-mediated intracellular delivery of clodronate is reported to selectively deplete mononuclear phagocytic cells such as macrophages that are important effector cells involved in the pathogenesis of neuropathies associated with demyelination and destruction of neuronal cells. Application of liposome-encapsulated clodronate (dichloromethylenediphosphonic acid disodium salt) is a method of choice to deplete macrophages to prevent such a neurodegeneration. In the present work, a comparison of an ion-exchange chromatography (IEC) and a capillary zone electrophoresis (CZE) method with indirect UV detection was performed and, based on the results of this comparison, a CZE assay was developed for quantitation of clodronate in mannosylated liposomes. This CZE method employed Nitroso-R salt (1-nitroso-2-naphthol-3,6-disulphonic acid disodium salt) as background electrolyte with UV detection of the analyte at 254 nm. The assay for the determination of clodronate in mannosylated liposomes after their solubilization in 10 mM Triton X-100 showed acceptable within-day precision (repeatability), day-to-day precision (reproducibility) and linearity in the target quantitation range of 0.5-10.0 mg ml-1. The method reported here can be used as part of the quality control during the preparation of liposome-encapsulated clodronate as a drug formulation for macrophage-mediated diseases.

Original languageEnglish
Pages (from-to)929-935
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume31
Issue number5
DOIs
Publication statusPublished - 1 Apr 2003

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Keywords

  • Capillary zone electrophoresis
  • Clodronate
  • Indirect UV detection
  • Ion-exchange chromatography
  • Mannosylated liposomes

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