Detection, identification and quantification of a new de-fluorinated impurity in casopitant mesylate drug substance during late phase development: An analytical challenge involving a multidisciplinary approach

During late phase development of the selective NK1 receptor antagonist casopitant mesylate, a de-fluorinated impurity was discovered and quantified by an orthogonal analytical approach, using NMR and LC–MS. A dedicated 19F NMR method was initially developed for first line identification and semi-qua...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2011-01, Vol.54 (1), p.67-73
Main Authors: Turco, Lucilla, Provera, Stefano, Curcuruto, Ornella, Bernabè, Elena, Nicoletti, Anna, Martini, Luca, Castoldi, Damiano, Cimarosti, Zadeo, Papini, Damiano, Marchioro, Carla, Dams, Riet
Format: Article
Language:English
Subjects:
Analysis
Analytical, structural and metabolic biochemistry
antagonists
Biological and medical sciences
Casopitant mesylate
Chemistry Techniques, Analytical
Chemistry, Pharmaceutical - methods
Chromatography, Liquid - methods
Drug Contamination
Drug development
drugs
Fluorine - chemistry
Fundamental and applied biological sciences. Psychology
General pharmacology
Halogenation
LC–MS
Magnetic Resonance Spectroscopy - methods
Mass Spectrometry - methods
Medical sciences
Models, Chemical
NMR spectroscopy
nuclear magnetic resonance spectroscopy
Orthogonal analytical control
patients
Pharmaceutical Preparations - chemistry
Pharmacology. Drug treatments
Piperazines - analysis
Piperidines - analysis
Quality Control
Reproducibility of Results
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Summary:During late phase development of the selective NK1 receptor antagonist casopitant mesylate, a de-fluorinated impurity was discovered and quantified by an orthogonal analytical approach, using NMR and LC–MS. A dedicated 19F NMR method was initially developed for first line identification and semi-quantification of the impurity. Subsequently, a more accurate quantification was achieved by means of a selective normal-phase LC–MS method, which was fully validated. The results obtained on the development batches of the drug substance were used by the project team to set up a suitable control strategy and ultimately to ensure patient safety and the progression of the project.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2010.08.010