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A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide

A global approach that is based on a combination of mass spectrometry (MS) and nuclear magnetic resonance (NMR) data has been developed for a complete and rapid understanding of drug degradation mixtures. We proposed a workflow based on a sample preparation protocol that is compatible to MS and NMR,...

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Autores principales: Palaric, Cécile, Molinié, Roland, Cailleu, Dominique, Fontaine, Jean-Xavier, Mathiron, David, Mesnard, François, Gut, Yoann, Renaud, Tristan, Petit, Alain, Pilard, Serge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539681/
https://www.ncbi.nlm.nih.gov/pubmed/31067700
http://dx.doi.org/10.3390/molecules24091764
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author Palaric, Cécile
Molinié, Roland
Cailleu, Dominique
Fontaine, Jean-Xavier
Mathiron, David
Mesnard, François
Gut, Yoann
Renaud, Tristan
Petit, Alain
Pilard, Serge
author_facet Palaric, Cécile
Molinié, Roland
Cailleu, Dominique
Fontaine, Jean-Xavier
Mathiron, David
Mesnard, François
Gut, Yoann
Renaud, Tristan
Petit, Alain
Pilard, Serge
author_sort Palaric, Cécile
collection PubMed
description A global approach that is based on a combination of mass spectrometry (MS) and nuclear magnetic resonance (NMR) data has been developed for a complete and rapid understanding of drug degradation mixtures. We proposed a workflow based on a sample preparation protocol that is compatible to MS and NMR, the selection of the most appropriate experiments for each technique, and the implementation of prediction software and multivariable analysis method for a better interpretation and correlation of MS and NMR spectra. We have demonstrated the efficient quantification of the remaining active pharmaceutical ingredient (API). The unambiguous characterization of degradation products (DPs) was reached while using the potential of ion mobility-mass spectrometry (IM-MS) for fragment ions filtering (HDMS(E)) and the implementation of two-dimensional (2D) NMR experiments with the non-uniform sampling (NUS) method. We have demonstrated the potential of quantitative NMR (qNMR) for the estimation of low level DPs. Finally, in order to simultaneously monitor multi-samples, the contribution of partial least squares (PLS) regression was evaluated. Our methodology was tested on three indapamide forced degradation conditions (acidic, basic, and oxidative) and it could be easily transposed in the drug development field to assist in the interpretation of complex mixtures (stability studies, impurities profiling, and biotransformation screening).
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spelling pubmed-65396812019-05-31 A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide Palaric, Cécile Molinié, Roland Cailleu, Dominique Fontaine, Jean-Xavier Mathiron, David Mesnard, François Gut, Yoann Renaud, Tristan Petit, Alain Pilard, Serge Molecules Article A global approach that is based on a combination of mass spectrometry (MS) and nuclear magnetic resonance (NMR) data has been developed for a complete and rapid understanding of drug degradation mixtures. We proposed a workflow based on a sample preparation protocol that is compatible to MS and NMR, the selection of the most appropriate experiments for each technique, and the implementation of prediction software and multivariable analysis method for a better interpretation and correlation of MS and NMR spectra. We have demonstrated the efficient quantification of the remaining active pharmaceutical ingredient (API). The unambiguous characterization of degradation products (DPs) was reached while using the potential of ion mobility-mass spectrometry (IM-MS) for fragment ions filtering (HDMS(E)) and the implementation of two-dimensional (2D) NMR experiments with the non-uniform sampling (NUS) method. We have demonstrated the potential of quantitative NMR (qNMR) for the estimation of low level DPs. Finally, in order to simultaneously monitor multi-samples, the contribution of partial least squares (PLS) regression was evaluated. Our methodology was tested on three indapamide forced degradation conditions (acidic, basic, and oxidative) and it could be easily transposed in the drug development field to assist in the interpretation of complex mixtures (stability studies, impurities profiling, and biotransformation screening). MDPI 2019-05-07 /pmc/articles/PMC6539681/ /pubmed/31067700 http://dx.doi.org/10.3390/molecules24091764 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Palaric, Cécile
Molinié, Roland
Cailleu, Dominique
Fontaine, Jean-Xavier
Mathiron, David
Mesnard, François
Gut, Yoann
Renaud, Tristan
Petit, Alain
Pilard, Serge
A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide
title A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide
title_full A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide
title_fullStr A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide
title_full_unstemmed A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide
title_short A Deeper Investigation of Drug Degradation Mixtures Using a Combination of MS and NMR Data: Application to Indapamide
title_sort deeper investigation of drug degradation mixtures using a combination of ms and nmr data: application to indapamide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539681/
https://www.ncbi.nlm.nih.gov/pubmed/31067700
http://dx.doi.org/10.3390/molecules24091764
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