Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

Application of 2D-NMR with Room Temperature NMR Probes for the Assessment of the Higher Order Structure of Filgrastim

Published

Author(s)

Robert G. Brinson, Houman Ghasriani, Derek Hodgson, Adams Kristie, Ian McEwen, Kang Chen, Yves Aubin, John P. Marino

Abstract

The higher order structure (HOS) of biotherapeutics is a critical quality attribute that can be evaluated by nuclear magnetic resonance (NMR) spectroscopy at atomic resolution. NMR spectral mapping of HOS can be used to establish HOS consistency of a biologic across manufacturing changes or to compare a biosimilar to an innovator reference product. A previous inter-laboratory study performed using filgrastim drug products demonstrated that two-dimensional (2D)-NMR 1HN-15NH heteronuclear correlation spectroscopy is a highly robust and precise method for mapping the HOS of biologic drugs at natural abundance using high sensitivity NMR ‘cold probes.’ Here, we demonstrate applicability of the 2D-NMR method to fingerprint the HOS of filgrastim products using lower sensitivity, room temperature NMR probes. Combined chemical shift deviation and principal component analysis are used to illustrate the performance and inter-laboratory precision of the 2D-NMR method when implemented on room temperature probes.
Citation
Journal of Pharmaceutical and Biomedical Analysis
Volume
141

Keywords

NMR, higher order structure, biologics, PCA, fingerprinting

Citation

Brinson, R. , Ghasriani, H. , Hodgson, D. , Kristie, A. , McEwen, I. , Chen, K. , Aubin, Y. and Marino, J. (2017), Application of 2D-NMR with Room Temperature NMR Probes for the Assessment of the Higher Order Structure of Filgrastim, Journal of Pharmaceutical and Biomedical Analysis, [online], https://doi.org/10.1016/j.jpba.2017.03.063 (Accessed July 16, 2024)

Issues

If you have any questions about this publication or are having problems accessing it, please contact reflib@nist.gov.

Created January 15, 2017, Updated February 13, 2020