Ion chromatography for the determination of sulfate in STEALTH® liposomes

An ion chromatography (IC) method has been validated for the assay of sulfate ion content in the STEALTH® liposome drug-delivery system (ALZA, Mountain View, CA, USA), which contains ammonium sulfate as an excipient. This method contains two assays. One assay determines the total sulfate ion content; the other determines the external sulfate ions. The total sulfate ion analysis measures the sulfate ion content of the formulation, inside and outside of the liposome. The analysis includes the disruption of the liposome bilayer with Triton-X, followed by dilution with 10% sucrose, and analysis using IC. The external sulfate analysis measures sulfate ions outside the liposome without disrupting the liposome structure. A neat sample of STEALTH® liposome drug-delivery system is filtered through a 0.02 μm filter, and the filtrate is analyzed by IC. Sulfate ion is resolved on an anion exchange column and detected by a conductivity detector. Quantitation is performed by linear regression analysis of peak areas from a standard curve of sulfate ion containing at least five standard points. The method was validated for specificity, linearity, accuracy/recovery, precision, and stability of the standard and the sample. The validated method has been applied to the quantification of sulfate ion in STEALTH® liposomes for product release and stability testing.