Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR
One unknown impurity (Imp-II) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2oylamino)ethyl]benzen...
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Published in | Journal of pharmaceutical analysis Vol. 7; no. 6; pp. 394 - 400 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
China
Elsevier B.V
01.12.2017
Chemical Research Department, Micro Labs Ltd, API Division, Bommasandra-Jigani Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India Xi'an Jiaotong University Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | One unknown impurity (Imp-II) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2oylamino)ethyl]benzene-l,2-diol (Imp-II) using the liquid chromatography-mass spectrophotometry (LC-MS) analysis. Imp-II was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C, DEPT (1D NMR), HSQC (2D NMR) and infrared spectroscopy (IR), and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification, the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit 〈 0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details. |
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Bibliography: | One unknown impurity (Imp-II) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2oylamino)ethyl]benzene-l,2-diol (Imp-II) using the liquid chromatography-mass spectrophotometry (LC-MS) analysis. Imp-II was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C, DEPT (1D NMR), HSQC (2D NMR) and infrared spectroscopy (IR), and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification, the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit 〈 0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details. 61-1484/R Isoproterenol hydrochloride;Impurities;HPLC;NMR ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2095-1779 2214-0883 |
DOI: | 10.1016/j.jpha.2017.05.002 |