Raman spectroscopy and multivariate analysis for the rapid discrimination between native-like and non-native states in freeze-dried protein formulations
| Autor: | Yvan Vander Heyden, Bart De Spiegeleer, Jean Paul Remon, Jean-Michel Roger, Laurent Hansen, Sigrid Pieters, Matthias D'Hondt, B. Palagos, Chris Vervaet, Thomas De Beer |
|---|---|
| Přispěvatelé: | Vrije Universiteit [Brussels] (VUB), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Laboratory of Drug Quality & Registration, Universiteit Gent, Laboratory of Pharmaceutical Process Analytical Technology, Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel (VUB), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro) |
| Předmět: |
Chemistry
Pharmaceutical Analytical chemistry Pharmaceutical Science 02 engineering and technology Spectrum Analysis Raman 01 natural sciences Protein Structure Secondary Excipients Chemometrics symbols.namesake Raman spectroscopy Multivariate analysis Partial least squares regression PROTEINE Side chain ANALYSE MULTIVARIEE Least-Squares Analysis Protein secondary structure LYOPHILISATION Second derivative Principal Component Analysis CONFORMATIONAL STATE L-Lactate Dehydrogenase Chemistry 010401 analytical chemistry MULTIVARIATE ANALYSIS LACTATE DEHYDROGENASE Proteins SPECTROSCOPIE General Medicine 021001 nanoscience & nanotechnology Linear discriminant analysis 0104 chemical sciences CONFORMATION Freeze Drying Principal component analysis [SDE]Environmental Sciences symbols RAMAN SPECTROSCOPY 0210 nano-technology FREEZE-DRYING PAT Biotechnology |
| Zdroj: | Vrije Universiteit Brussel European Journal of Pharmaceutics and Biopharmaceutics European Journal of Pharmaceutics and Biopharmaceutics, Elsevier, 2013, 85 (2), p. 263-p. 271. ⟨10.1016/j.ejpb.2013.03.035⟩ |
| ISSN: | 0939-6411 |
| Popis: | This study investigates whether Raman spectroscopy combined with multivariate analysis (MVA) enables a rapid and direct differentiation between two classes of conformational states, i.e., native-like and non-native proteins, in freeze-dried formulations. A data set comprising of 99 spectra, both from native-like and various types of non-native freeze-dried protein formulations, was obtained by freeze-drying lactate dehydrogenase (LDH) as model protein under various conditions. Changes in the secondary structure in the solid freeze-dried proteins were determined through visual interpretation of the blank corrected second derivative amide I band in the ATR-FTIR spectra (further called FTIR spectra) and served as an independent reference to assign class labels. Exploratory analysis and supervised classification, using Principal Components Analysis (PCA) and Partial Least Squares – Linear Discriminant Analysis (PLS–LDA), respectively, revealed that Raman spectroscopy is with 95% accuracy able to correctly discriminate between native-like and non-native states in the tested freeze-dried LDH formulations. Backbone (i.e., amide III) and side chain sensitive spectral regions proved important for making the discrimination between both classes. As discrimination was not influenced by the spectral signals from the tested excipients, there was no need for blank corrections. The Raman model may allow direct and automated analysis of the investigated quality attribute, opening possibilities for a real time and in-line quality indication as a future step. However, the sensitivity of the method should be further investigated and where possible improved. |
| Databáze: | OpenAIRE |
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