Structural analysis of an impurity of the drug landiolol |
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Authors: | Michal ?tujber Sagar Beldar Constantin Rabong Igor Beseda Martin Breza Tibor Liptaj |
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Institution: | 1. Department of NMR and Mass Spectroscopy, Slovak University of Technology in Bratislava, , Radlinského 9, SK‐812 37 Bratislava, Slovak Republic;2. Institute of Applied Synthetic Chemistry, Vienna University of Technology, , A‐1060 Vienna, Austria;3. A1synth Ltd., , SK‐812 37 Bratislava, Slovak Republic;4. Department of Physical Chemistry, Slovak University of Technology in Bratislava, , SK‐812 37 Bratislava, Slovak Republic |
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Abstract: | In a course of development and preparation of landiolol (1a), a known ultra‐short‐acting β‐blocker, process quality control by HPLC and LC‐MS analysis consistently showed an impurity peak ranging from 0.05% to 0.15 % and exhibiting a molecular mass m/z 887. To identify the hitherto unknown impurity, we prepared one of the possible landiolol derivatives with the same molecular mass for proper spectral characterization (NMR and MS). Its equivalence with the unknown impurity was then confirmed by LC‐MS analysis. Ultimately, using fragmentation patterns in LC‐MS and selective two‐dimensional NMR experiments, the structure of the impurity was assigned as (4S)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl]methyl 3‐{4‐(2S)‐2‐hydroxy‐3‐(3‐{4‐(2S)‐2‐hydroxy‐3‐(2‐{(morpholin‐4‐yl)carbonyl]amino}ethyl)amino]propoxy]phenyl}‐N‐(2‐{(morpholin‐4‐yl)carbonyl]amino}ethyl)propanamido)propoxy]phenyl}propanoate (2). It was found that the impurity was present in two rotameric forms at room temperature. The synthesis and NMR characterization of (2) are discussed. Copyright © 2014 John Wiley & Sons, Ltd. |
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Keywords: | NMR 1H 13C landiolol DPFGSE band selective 2D NMR DFT |
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