Isolation and identification of a major impurity in a new bulk drug candidate by preparative LC, ESI-MS(n), LC-MS-MS, and NMR |
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Authors: | Li Ning Yang Jing Qin Fang Li Famei Gong Ping |
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Institution: | Department of Analytical Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, China. |
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Abstract: | A simple preparative liquid chromatography (LC) method is developed to isolate a major impurity in a new bulk drug candidate, 6-bromo-4-(carbamidinemethyl)-5-hydroxy-1-methyl-2-(phenylthiomethyl)-1H-indole-3-carboxylic acid ethyl ester hydrochloride monohydrate (carmidole). The carmidole solution for preparation is exposed to daylight before isolation. Based on the electrospray ionization (ESI)-mass spectroscopy (MS(n)) spectral data of the impurity fraction and carmidole, the impurity is preliminarily characterized as 6-bromo-4-(carbamidinemethyl)-5-hydroxy-1-methyl-2-methyl-1H-indole-3-carboxylic acid ethyl ester. LC-MS-MS is used to analyze a carmidole sample. The impurity, lyophilate, is obtained from the fraction of preparative LC, and the impurity standard is synthesized. By comparison of the retention times of high-performance liquid chromatography, ESI-MS(n), and (1)H-nuclear magnetic resonance of the impurity lyophilate with impurity standard and carmidole itself, the structure of the impurity is confirmed and its formation is discussed. |
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