Monitoring stability indicating impurities and aldehyde content in lipid nanoparticle raw material and formulated drugs.

Autor: Birdsall RE; Waters Corporation, 34 Maple St. Milford, MA 01757, USA. Electronic address: Robert_Birdsall@waters.com., Han D; Waters Corporation, 34 Maple St. Milford, MA 01757, USA., DeLaney K; Waters Corporation, 34 Maple St. Milford, MA 01757, USA., Kowalczyk A; Acuitas Therapeutics, 6190 Agronomy Rd. Suite 405, Vancouver, BC, V6T 1Z3, Canada., Cojocaru R; Acuitas Therapeutics, 6190 Agronomy Rd. Suite 405, Vancouver, BC, V6T 1Z3, Canada., Lauber M; Waters Corporation, 34 Maple St. Milford, MA 01757, USA., Huray JL; Acuitas Therapeutics, 6190 Agronomy Rd. Suite 405, Vancouver, BC, V6T 1Z3, Canada.
Jazyk: angličtina
Zdroj: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2024 Feb 15; Vol. 1234, pp. 124005. Date of Electronic Publication: 2024 Jan 18.
DOI: 10.1016/j.jchromb.2024.124005
Abstrakt: Lipid nanoparticles (LNPs) are designed to protect and transport sensitive payloads or active pharmaceutical ingredients as part of new therapeutic modalities. As a multi-component particle, a high degree of quality control is necessary to ensure raw materials are free of critical impurities that could adversely impact the drug product. In this study, we demonstrate a reversed phase liquid chromatography method hyphenated with a single quadrupole mass spectrometer (RPLC-MS) as an alternative platform to methods that incorporate evaporative light scattering or charged aerosol detectors in the detection and quantitation of critical impurities associated with LNPs. The proposed RPLC-MS method offers an increase of up to 2 orders of magnitude in dynamic range and 3 orders of magnitude in sensitivity in the analysis of impurities associated with LNPs compared to conventional detectors. Access to complementary mass data enabled the detection and identification of stability indicating impurities as part of stress studies carried out on an ionizable lipid. In addition to confirmation of peak identity, complementary mass data was also used to assess residual aldehydes in raw material and formulated LNPs in accordance with regulatory guidance. Following derivatization using 2,4-dinitrophenylhydrazine, aldehyde content in the ionizable lipid raw material was determined to exceed the reporting threshold of 0.05% in 30% of the test cases. The experimental findings observed in this study demonstrate the utility of the proposed RPLC-MS method in the identification and monitoring of stability-indicating attributes associated with LNPs as part of current Good Manufacturing Practices for improved consumer safety in drug products.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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