title: Identification, preparation and UHPLC determination of process-related impurity in zolmitriptan.
abstract: A new impurity was detected and determined using gradient ion-pair UHPLC method with UV detection in zolmitriptan (ZOL). Using MS, NMR and IR study the impurity was identified as (4S,4'S)-4,4'-(2,2'-(4-(dimethylamino)butane-1,1-diyl)bis(3-(2-(dimethylamino) ethyl)-1H-indole-5,2-diyl))bis(methylene)di(oxazolidin-2-one) (ZOL-dimer). The standard of ZOL-dimer was consequently prepared via organic synthesis followed by semipreparative HPLC purification. The UHPLC method was optimized in order to selectively detect and quantify other known and unknown process-related impurities and degradation products of ZOL as well. The presented method which was validated with respect to linearity, accuracy, precision and selectivity has an advantage of a very quick UHPLC chromatographic separation (less than 7 min including re-equilibration time) and therefore is highly suitable for routine analysis of related substances and stability studies of ZOL.
authors: Zentiva, a.s. Praha, U Kabelovny 130, 102 37 Praha 10, Czech Republic. hplc@hplc.cz
authors: Michal
authors: M
authors: Douša
authors: Petr
authors: P
authors: Gibala
authors: Stanislav
authors: S
authors: Rádl
authors: Ondřej
authors: O
authors: Klecán
authors: Zuzana
authors: Z
authors: Mandelová
authors: Jiří
authors: J
authors: Břicháč
authors: Tomáš
authors: T
authors: Pekárek
mesh_terms: D060326:Chemistry Techniques, Synthetic / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004340:Drug Contamination; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D010080:Oxazoles / Q000302:isolation & purification; D023303:Oxazolidinones / Q000737:chemistry* / Q000302:isolation & purification; D013055:Spectrophotometry, Infrared / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D014363:Tryptamines / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D010080:Oxazoles; D023303:Oxazolidinones; D014363:Tryptamines; C089750:zolmitriptan