2021 FDA Science Forum
A Standard Test Method for Lipid Quantitation in Liposomal Formulations Using Ultra-High-Performance Liquid Chromatography with Triple Quadrupole Mass Spectrometry (UHPLC-TQMS)
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Contributing OfficeNational Center for Toxicological Research
Abstract
With rapid developments in nanotechnology, there has been a steady increase in submissions to FDA of products containing nanomaterials for drug delivery, gene delivery, and medical devices. Liposomes are vesicles of nanoscale dimensions, composed of lipid bilayers, used as carriers for small molecules and constitute a third of the drug products submission utilizing nanotechnology. There is a lack of documentary and reference material standards to assess the critical quality attributes that facilitate regulatory review and market entry of safe and effective products. Lipid composition and concentration are key attributes in determining the quality and efficacy of a liposomal drug product, as they influence the stability of liposomes, drug incorporation, release, and pharmacokinetic properties. FDA Nanotechnology Task Force Standards sub-committee has identified the development of a standard test method to quantify lipid components in liposomal formulations as a high priority need for collaborative consensus standard development.
The development of a test method standard for the quantitation of lipids in liposomal formulations using ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-TQMS) will be presented in this poster. This test method is specific for liposomal formulations consisting of cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] and hydrogenated (soy) L-?-phosphatidylcholine. UHPLC-TQMS offers higher selectivity, sensitivity, wide linear range of quantitation, high signal-to-noise ratio (S/N), and accuracy, compared to other contemporary techniques utilizing universal detectors, thereby allowing robust and reproducible quantitation of the analytes. This test method is currently undergoing ASTM International E56-08 sub-committee balloting after significant testing in the laboratory, and review by stakeholders. Once finalized this test method standard will benefit industry in ascertaining quality assessment of liposomal formulations and in monitoring batch-to-batch consistency. The development of this standard is highly relevant for quality control of liposomal formulation, and supports FDA’s mission to protect and promote public health.
