Principal Scientist Waters Corporation Milford, Massachusetts
Research into and the pharmacology of lipid nanoparticles is exploding because of the proven effectiveness of encapsulated small interfering RNA (siRNA) and new mRNA-based vaccines, the success of which depends on the availability of a safe and efficient delivery vehicle. When measuring the composition of an LNP nucleic acid drug, the disruption of lipid to nucleic acid interactions is paramount. For this reason, there remains a need for sample preparation techniques and analytical approaches that would facilitate both the analysis of lipid components and the nucleic acid drug substance. Our approach demonstrates that anion exchange (AX) solid phase extraction (SPE) can be used to partition the lipids away from the retained nucleic acid. The elution of the nucleic acid is facilitated by use of high pH solutions. The approach demonstrates the ability to prepare purified lipid and nucleic acid samples ready for subsequent chromatographic and mass spectrometric analysis.
Learning Objectives:
Upon completion, participant will be able to fractionate a lipid nanoparticle drug product into the lipid components and the nucleic acid component.
Upon completion, participant will be able to prepare a purified nucleic acid sample for subsequent chromatographic and mass spectrometric analysis or for nuclease digestion reactions and oligo mapping experiments.
Upon completion, participant will be able to identify individual lipid components to determine the molar ratio of each in the LNP formulation.
