Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2026 Jan;418(1):179-188.
doi: 10.1007/s00216-025-06210-6. Epub 2025 Dec 11.

Measuring ethanol clearance in lipid nanoparticles and liposomes by benchtop NMR

Nicholas Cunningham  1 , Richard R Rustandi  1 , David Boyd  2 , Matthew Schombs  1 , Adam T Sutton  3
Affiliations

Measuring ethanol clearance in lipid nanoparticles and liposomes by benchtop NMR

Nicholas Cunningham et al. Anal Bioanal Chem. 2026 Jan.

Erratum in

Abstract

A benchtop nuclear magnetic resonance (NMR) method for quantifying ethanol in liposomal emulsions and mRNA-lipid nanoparticle (mRNA-LNP) systems is presented. The method development performed demonstrates the feasibility of benchtop NMR as an alternative to gas chromatography (GC) for ethanol quantitation, offering advantages such as simpler operation, reduced instrument maintenance, and minimal sample preparation. The use of benchtop NMR was assessed in terms of accuracy, linearity, precision, repeatability, and sensitivity with the limit of quantitation (LOQ) being ≤ 25 mg/mL, which is well below the necessary 5000 mg/mL value established for Class 3 solvents by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). This study also highlights the utility of benchtop NMR as a process analytical technology (PAT) tool, providing insights into the ethanol clearance efficiency of the mRNA-LNP process from initial lipid dissolution to the end of the purification steps that lead to process modifications. The method shown here can be applied to measuring ethanol in various lipid formulations as well as many other matrices containing large molecules that often interfere in other methods.

Keywords: Benchtop NMR spectroscopy; Lipid emulsions; Residual ethanol; mRNA-lipid nanoparticles.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: All authors are/were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may potentially own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA.

References

    1. Raman M, Almutairdi A, Mulesa L, Alberda C, Beattie C, Gramlich L. Parenteral nutrition and lipids. Nutrients. 2017;9(4):388. - DOI - PubMed - PMC
    1. Wretlind A. Recollections of pioneers in nutrition: landmarks in the development of parenteral nutrition. J Am Coll Nutr. 1992;11(4):366–73. - DOI - PubMed
    1. Barsoum N, Kleeman C. Now and then, the history of parenteral fluid administration. Am J Nephrol. 2002;22(2–3):284–9. - DOI - PubMed
    1. Bangham AD, Horne RW. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J Mol Biol. 1964;8(5):660-IN610. - DOI - PubMed
    1. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13(1):238–52. - DOI - PubMed

MeSH terms

LinkOut - more resources