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Cited by 24Analytical Methods in PharmaceuticalsNanoparticle-Based Drug DeliveryLipid Membrane Structure and Behavior

Quantitative analysis of cholesterol oxidation products and desmosterol in parenteral liposomal pharmaceutical formulations

Wang, Changguang, Siriwardane, Dumindika A., Jiang, Wenlei, Mudalige, Thilak·2019·International Journal of Pharmaceutics
DOI 10.1016/j.ijpharm.2019.118576
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Abstract

Cholesterol is one of the major structural constituents in a liposomal bilayer. Cholesterol is susceptible to various reactions in the presence of oxygen, heat, light, certain metals, and radicals during manufacturing or storage, which may cause to generate cholesterol oxidation products (COPs). Herein, we report the development of a liquid chromatography-mass spectrometry based analytical method for screening and quantitating COPs present in liposomal parenteral pharmaceutical formulations (LPFs) from four different vendors. We detected and quantitated six COPs and desmosterol in LPFs, and desmosterol is an intermediate of cholesterol biosynthesis. 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-keto-cholesterol, and desmosterol were the major cholesterol-related impurities in LPFs. COPs were not detected in any of USP/NF grade cholesterol raw materials, implying that COPs were generated during liposome manufacturing and/or storage. This validated method presented here can be used to quantify cholesterol-related impurities present in liposomal pharmaceutical formulations to ensure the quality and the safety of liposomal pharmaceutical formulations.

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  • Lipid oxidation can occur in unsaturated fatty acid moieties, which are not present in Comirnaty and mRNA-1273, and with cholesterol, potentially as a result of a hydroperoxide attack or an impurity present in the PEG-group of PEG2000-C-DMG.

    “Lipid oxidation can occur in unsaturated fatty acid moieties (not present in Comirnaty and mRNA-1273) and with cholesterol, potentially as a result of a hydroperoxide attack, an impurity present in the PEG-group of PEG2000-C-DMG (Jaeger et al., 1994, Wang et al., 2019).”

    From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Wang et al., 2019

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Authors
Wang, C., Siriwardane, D. A., Jiang, W., & Mudalige, T.
Affiliations
United States Food and Drug Administration (US)
Corresponding author
  • Jiang, Wenlei
  • Mudalige, Thilak
ORCID
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2019-10
Volume
569
Pages
118576
ISSN
0378-5173 (ISSN-L)
DOI
10.1016/j.ijpharm.2019.118576
OpenAlex
W2966104617
Cited by
24
References
42
Citations by year
2026: 3 · 2025: 2 · 2024: 8 · 2023: 4 · 2021: 6 · 2020: 1
FWCI
0.98
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • International Journal of Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
Keywords
cholesterol oxidation products, desmosterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, quality control, LC-MS method development
MeSH terms
Cholesterol, Chromatography, High Pressure Liquid, Liposomes, Oxidation-Reduction, Parenteral Nutrition, Mass Spectrometry

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