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.
Halmos
Z
Z
Chemical Works of Gedeon Richter Ltd., Budapest, Hungary.
Szántay
C
C
Brlik
J
J
Csehi
A
A
Varga
K
K
Horváth
P
P
Kislaki
M
M
Domány
G
G
Nemes
A
A
Görög
S
S
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