Estimation of impurity profiles of drugs and related materials Part 15. Identification of minor impurities in cimetidine.
Besides several known impurities in cimetidine, two additional compounds at levels below 0.1% were detected by ion-pair reversed-phase high-performance liquid chromatography (HPLC). The impurities were isolated from crude cimetidine using normal-phase preparative HPLC. 1H and 13C NMR and mass spectrometric investigations revealed the structures of the impurities to be 2,5-bis[(N'-cyano-N"-methyl)guanidinoethylthiomethyl]-4-methylimid azole (VII) and 1,8-bis[(N'-cyano-N"-methyl)guanidino]-3,6-dithiaoctane (VIII). These structures were verified by synthesis of the impurities and comparison of the spectra and chromatographic (HPLC and TLC) retention data of the isolated and synthesized materials.
Chemical Works of Gedeon Richter Ltd., Budapest, Hungary.
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Halmos
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Szántay
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Csehi
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Varga
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Horváth
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Kislaki
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Domány
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Nemes
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Görög
D000897:Anti-Ulcer Agents / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000031:analogs & derivatives / Q000032:analysis* / Q000737:chemistry; D004340:Drug Contamination; D007093:Imidazoles / Q000138:chemical synthesis / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008760:Methylguanidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification
C103426:1,8-bis((N'-cyano-N''-methyl)guanidino)3,6-dithiaoctane; C103425:2,5-bis((N'-cyano-N''-methyl)guanidinoethylthiomethyl)-4-methylimidazole; D000897:Anti-Ulcer Agents; D007093:Imidazoles; D008760:Methylguanidine; D002927:Cimetidine