TY - JOUR
T1 - Consistency of a dialyzable leucocyte extract manufactured at GMP facilities by nuclear magnetic resonance spectroscopy
AU - Herbert-Pucheta, José Enrique
AU - López-Morales, Carlos A.
AU - Medina-Rivero, Emilio
AU - Estrada-Parra, Sergio
AU - Pérez-Tapia, Sonia Mayra
AU - Zepeda-Vallejo, L. Gerardo
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/3/20
Y1 - 2021/3/20
N2 - 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.
AB - 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.
KW - Complex drugs
KW - Dialyzable leucocyte extracts
KW - Diffusion coefficient distributions
KW - NMR consistency
KW - Polydispersity indexes
KW - Reproducibility and homogeneity
UR - http://www.scopus.com/inward/record.url?scp=85100417238&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2021.113940
DO - 10.1016/j.jpba.2021.113940
M3 - Artículo
C2 - 33549874
AN - SCOPUS:85100417238
SN - 0731-7085
VL - 196
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
M1 - 113940
ER -