title: Structural analysis of an impurity of the drug landiolol.
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.
authors.affiliation: Department of NMR and Mass Spectroscopy, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37, Bratislava, Slovak Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Štujber
authors.forename: Sagar
authors.initials: S
authors.lastname: Beldar
authors.forename: Constantin
authors.initials: C
authors.lastname: Rabong
authors.forename: Igor
authors.initials: I
authors.lastname: Beseda
authors.forename: Martin
authors.initials: M
authors.lastname: Breza
authors.forename: Tibor
authors.initials: T
authors.lastname: Liptaj
mesh_terms: D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009025:Morpholines / Q000032:analysis* / Q000737:chemistry*; D014508:Urea / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry
chemical_list: D009025:Morpholines; C077049:landiolol; D014508:Urea
keywords: 13C; 1H; DFT; DPFGSE; NMR; band selective 2D NMR; landiolol