Ion quantification in liposomal drug products using high performance liquid chromatography

Area of Science:

• Pharmaceutical analysis
• Analytical chemistry
• Liposome technology

Background:

• Liposomal drug formulations require precise ion quantification for quality control.
• Existing methods for ion analysis in liposomes can be time-consuming and lack sensitivity.

Purpose of the Study:

• To develop and optimize a straightforward, accurate analytical method for quantifying total, internal, and external ions in drug-loaded liposomes.
• To establish a method for assessing compositional similarity between generic and reference liposomal products, such as Doxil.

Main Methods:

• Utilized high-performance liquid chromatography (HPLC) with a charged aerosol detector for ion quantification.
• Employed lyophilization to disrupt liposomes for total ion measurement.
• Used membrane centrifugation to separate external ions without liposome disruption.

Main Results:

• Successfully quantified ammonium and sulfate ions in Doxil, and extrapolated the method for calcium, acetate, and other ions in various liposomal formulations.
• Achieved improved lower limits of detection and quantification compared to traditional methods.
• Validated analytical measurements using stoichiometry based on doxorubicin crystallization.

Conclusions:

• The developed HPLC method is rapid, accurate, and sensitive for ion quantitation in liposomal products.
• This facile approach is crucial for establishing compositional similarity for follow-on versions of liposomal drugs like Doxil.
• The method offers a significant advancement in the analytical characterization of liposomal formulations.