A Deformulating Multi-Attribute SEC Method for Simultaneous Quantification of Total RNA, Conjugated Antibody, and Free Antibody in Targeted Lipid Nanoparticles

An online deformulating SE-HPLC workflow quantifies total RNA, conjugated antibody, and free antibody from 5 L of targeted lipid nanoparticle samples with linear response, 88–122% spike recoveries, and <5% precision.

• Why it matters: Targeted lipid nanoparticles require measuring both encapsulated RNA and surface-associated targeting antibodies, but conventional assays can be confounded by nanoparticle scattering and matrix effects, especially for distinguishing conjugated from free antibody.
• What they did: The method uses online disruption with a mobile phase containing sodium dodecyl sulfate and isopropanol after injection, then separates RNA (UV260) and antibody (UV280 or intrinsic fluorescence) for simultaneous quantification.
• The result: In purified tLNP formulations, it enabled concurrent assessment of total RNA and conjugated antibody and confirmed no detectable free antibody after purification, supporting practical multi-attribute characterization with standard HPLC instrumentation.

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