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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/5/2415 |
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| author | Ao Xu Yunlin Xue Yuyu Zeng Jing Li Huiling Zhou Zhen Wang Yin Chen Hui Chen Jian Jin Tao Zhuang |
| author_facet | Ao Xu Yunlin Xue Yuyu Zeng Jing Li Huiling Zhou Zhen Wang Yin Chen Hui Chen Jian Jin Tao Zhuang |
| author_sort | Ao Xu |
| collection | DOAJ |
| 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 (<sup>1</sup>H, <sup>13</sup>C, and DEPT), and 2D-NMR (<sup>1</sup>H-<sup>1</sup>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. |
| first_indexed | 2024-03-11T07:15:44Z |
| format | Article |
| id | doaj.art-a2fe1bafb9bf4766936eff7a0fe97b7a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T07:15:44Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a2fe1bafb9bf4766936eff7a0fe97b7a2023-11-17T08:16:22ZengMDPI AGMolecules1420-30492023-03-01285241510.3390/molecules28052415Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC MethodAo Xu0Yunlin Xue1Yuyu Zeng2Jing Li3Huiling Zhou4Zhen Wang5Yin Chen6Hui Chen7Jian Jin8Tao Zhuang9Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaXuzhou Institute for Food and Drug Control, Xuzhou 221000, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaJiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang 222005, ChinaFurosemide 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 (<sup>1</sup>H, <sup>13</sup>C, and DEPT), and 2D-NMR (<sup>1</sup>H-<sup>1</sup>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.https://www.mdpi.com/1420-3049/28/5/2415furosemideprocess-related impuritycharacterizationQ-TOF/LC–MS and NMRmethod validation |
| spellingShingle | Ao Xu Yunlin Xue Yuyu Zeng Jing Li Huiling Zhou Zhen Wang Yin Chen Hui Chen Jian Jin Tao Zhuang Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method Molecules furosemide process-related impurity characterization Q-TOF/LC–MS and NMR method validation |
| 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 | furosemide process-related impurity characterization Q-TOF/LC–MS and NMR method validation |
| url | https://www.mdpi.com/1420-3049/28/5/2415 |
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