Robust and accurate methods are needed for the separation and quantification of free and liposome-associated drugs in order to understand the quality, efficacy, and safety of liposomal drug preparations. A capillary electrophoresis (CE) with UV-Vis detection method was developed for the simultaneous separation and quantification of free and liposome-associated drug using a doxorubicin-containing liposome formulation as the model drug. Using a high-sensitivity detection cell, the doxorubicin CE detection sensitivity was enhanced about 10-fold compared to the conventional on-column UV-Vis detection with a 75 µm i.d. capillary column. Separation of free drug and the liposome-associated drug is based on their electrophoretic mobility difference in the electric field. The optimal separation of free doxorubicin from liposome-associated doxorubicin with minimal perturbation of liposomes in phosphate buffer was accomplished. The developed CE method was applied to study the drug leakage and the physical stability of liposomal formulations in mouse plasma. The liposomal formulation was diluted to the appropriate concentrations in phosphate buffer and incubated with mouse plasma before CE analysis. The stability of liposomal formulations in plasma was characterized by drug leakage that was studied by quantifying the free doxorubicin. Our data showed that there is no significant drug leakage (&lt; 1% of free doxorubicin) for liposomal doxorubicin formulations in mouse plasma for 24 h at 37 °C.  The results obtained with the doxorubicin hydrochloride liposome formulation demonstrate that CE with UV-Vis detection is a promising technique for use in early liposomal drug development as well as in quality control.<br/>

Development of a robust capillary electrophoresis methodology for direct quantification of free doxorubicin in liposomal doxorubicin formulations in plasma

256th National Meeting (2018)

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