1. Consistency of a dialyzable leucocyte extract manufactured at GMP facilities by nuclear magnetic resonance spectroscopy
- Author
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Sonia Mayra Pérez-Tapia, Carlos A. López-Morales, Sergio Estrada-Parra, José Enrique Herbert-Pucheta, L. Gerardo Zepeda-Vallejo, and Emilio Medina-Rivero
- Subjects
Magnetic Resonance Spectroscopy ,Clinical Biochemistry ,Dispersity ,Pharmaceutical Science ,Peptide ,Transfer Factor ,01 natural sciences ,Analytical Chemistry ,Turn (biochemistry) ,Consistency (statistics) ,Drug Discovery ,Humans ,Spectroscopy ,chemistry.chemical_classification ,Reproducibility ,Chromatography ,010405 organic chemistry ,Chemistry ,Plant Extracts ,Homogeneity (statistics) ,010401 analytical chemistry ,Reproducibility of Results ,Nuclear magnetic resonance spectroscopy ,0104 chemical sciences ,Molecular Weight ,Heteronuclear molecule - Abstract
The present work describes the development and validation of a first report including several non-invasive NMR schemes to identify parameters as local chemical environments, homo- and heteronuclear site-specific spin correlations, diffusion coefficient-dependent polydispersity indexes and quantification of identified peptide entities that composes a commercial human Dialyzable Leucocyte Extract (DLE), Transferon, an oral liquid formulation of low-molecular-weight peptides. The above parameters were useful indicators to verify reproducibility, consistency and homogeneity among the DLE batches manufactured at Good Manufacturing Practice (GMP) facilities and for batch-releasing purposes in a quality control laboratory. The results showed that peptide identity of the DLE is represented with both high reproducible one-dimensional proton spectra and diffusion coefficient distributions that predicts in turn a weight-average molecular weight of around 6.7-7.4 kDa and a mean polydispersity index of 1.13. The obtained NMR peptide fingerprint of the analyzed DLE allowed to i) confirm its structural homogeneity by line-shape analysis, ii) identify and quantify its peptide content within the total solution with qNMR methods iii) to confirm the robustness of the technique as a feasible alternative for routine analysis of Natural or non-Natural Complex Drugs, such as DLEs.
- Published
- 2020