Estimation of impurity profiles of drugs and related materials .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. H-1 and C-13 NMR and mass spectrometric investigations revealed the structures of the impurities to be 2,5-bis[(N'-cyano-N ''-methyl)guanidinoethylthiomethyl]-4-methylimidazole (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.