Forced degradation of fingolimod: effect of co-solvent and characterization of degradation products by UHPLC-Q-TOF-MS/MS and 1H NMR.
J Pharm Biomed Anal
; 115: 388-94, 2015 Nov 10.
Article
en En
| MEDLINE
| ID: mdl-26279369
Fingolimod (FGL), an immunomodulator drug for treating multiple sclerosis, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per International Conference on Harmonization specified conditions. The drug showed extensive degradation under base hydrolysis, however, it was stable under all other conditions. A total of three degradation products (DPs) were observed. The chromatographic separation of the drug and its degradation products was achieved on a Fortis C18 (100×2.1mm, 1.7µm) column with a mobile phase composed of 0.1% formic acid (Solvent A) and acetonitrile (Solvent B) in gradient mode. All the DPs were identified and characterized by liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) in combination with accurate mass measurements. The major DP was isolated and characterized by Nuclear Magnetic resonance spectroscopy. This is a typical case of degradation where acetonitrile used as co-solvent in stress studies, reacts with FGL in base hydrolytic conditions to produce acetylated DPs. Hence, it can be suggested that acetonitrile is not preferable as a co-solvent for stress degradation of FGL. The developed UHPLC method was validated as per ICH guidelines.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Solventes
/
Cromatografía Liquida
/
Tecnología Farmacéutica
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Espectrometría de Masas en Tándem
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Espectroscopía de Protones por Resonancia Magnética
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Clorhidrato de Fingolimod
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Factores Inmunológicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Pharm Biomed Anal
Año:
2015
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Reino Unido