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Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method

Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) meth...

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Autores principales: Xu, Ao, Xue, Yunlin, Zeng, Yuyu, Li, Jing, Zhou, Huiling, Wang, Zhen, Chen, Yin, Chen, Hui, Jin, Jian, Zhuang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005432/
https://www.ncbi.nlm.nih.gov/pubmed/36903659
http://dx.doi.org/10.3390/molecules28052415
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author Xu, Ao
Xue, Yunlin
Zeng, Yuyu
Li, Jing
Zhou, Huiling
Wang, Zhen
Chen, Yin
Chen, Hui
Jin, Jian
Zhuang, Tao
author_facet Xu, Ao
Xue, Yunlin
Zeng, Yuyu
Li, Jing
Zhou, Huiling
Wang, Zhen
Chen, Yin
Chen, Hui
Jin, Jian
Zhuang, Tao
author_sort Xu, Ao
collection PubMed
description Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) method. The new impurity was isolated and characterized by comprehensive analysis of FT-IR, Q-TOF/LC-MS, 1D-NMR ((1)H, (13)C, and DEPT), and 2D-NMR ((1)H-(1)H-COSY, HSQC, and HMBC) spectroscopy data. The possible formation pathway of impurity G was also discussed in detail. Moreover, a novel HPLC method was developed and validated for the determination of impurity G and the other six known impurities registered in the European Pharmacopoeia as per ICH guidelines. The HPLC method was validated with respect to system suitability, linearity, the limit of quantitation, the limit of detection, precision, accuracy, and robustness. The characterization of impurity G and the validation of its quantitative HPLC method were reported for the first time in this paper. Finally, the toxicological properties of impurity G were predicted by the in silico webserver ProTox-II.
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spelling pubmed-100054322023-03-11 Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method Xu, Ao Xue, Yunlin Zeng, Yuyu Li, Jing Zhou, Huiling Wang, Zhen Chen, Yin Chen, Hui Jin, Jian Zhuang, Tao Molecules Article Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) method. The new impurity was isolated and characterized by comprehensive analysis of FT-IR, Q-TOF/LC-MS, 1D-NMR ((1)H, (13)C, and DEPT), and 2D-NMR ((1)H-(1)H-COSY, HSQC, and HMBC) spectroscopy data. The possible formation pathway of impurity G was also discussed in detail. Moreover, a novel HPLC method was developed and validated for the determination of impurity G and the other six known impurities registered in the European Pharmacopoeia as per ICH guidelines. The HPLC method was validated with respect to system suitability, linearity, the limit of quantitation, the limit of detection, precision, accuracy, and robustness. The characterization of impurity G and the validation of its quantitative HPLC method were reported for the first time in this paper. Finally, the toxicological properties of impurity G were predicted by the in silico webserver ProTox-II. MDPI 2023-03-06 /pmc/articles/PMC10005432/ /pubmed/36903659 http://dx.doi.org/10.3390/molecules28052415 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Ao
Xue, Yunlin
Zeng, Yuyu
Li, Jing
Zhou, Huiling
Wang, Zhen
Chen, Yin
Chen, Hui
Jin, Jian
Zhuang, Tao
Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method
title Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method
title_full Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method
title_fullStr Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method
title_full_unstemmed Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method
title_short Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method
title_sort isolation and characterization of an unknown process-related impurity in furosemide and validation of a new hplc method
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10005432/
https://www.ncbi.nlm.nih.gov/pubmed/36903659
http://dx.doi.org/10.3390/molecules28052415
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