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 (19)F 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.
Turco
Lucilla
L
Analytical Chemistry, GlaxoSmithKline Medicines Research Centre, Via Fleming 4, 37135 Verona, Italy. lucilla.turco@aptuit.com
Provera
Stefano
S
Curcuruto
Ornella
O
Bernabè
Elena
E
Nicoletti
Anna
A
Martini
Luca
L
Castoldi
Damiano
D
Cimarosti
Zadeo
Z
Papini
Damiano
D
Marchioro
Carla
C
Dams
Riet
R
D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods; D004340:Drug Contamination; D005461:Fluorine / Q000737:chemistry*; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010879:Piperazines / Q000032:analysis*; D010880:Piperidines / Q000032:analysis*; D011786:Quality Control; D015203:Reproducibility of Results; D014508:Urea
D005461:Fluorine; D004364:Pharmaceutical Preparations; D010879:Piperazines; D010880:Piperidines; C531951:casopitant; D014508:Urea