ESTIMATION OF IMPURITY PROFILES OF DRUGS AND RELATED MATERIALS .15. IDENTIFICATION OF MINOR IMPURITIES IN CIMETIDINE

Besides several known impurities in cimetidine, two additional compoun ds 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 o f the impurities to be 2,5-bis[(N'-cyano-N methyl)guanidinoethylthiome thyl]-4-methylimidazole (VII) and 1,8-bis[(N'-cyano-N ''-methyl)guanid ino]-3,6-dithiaoctane (VIII). These structures were verified by synthe sis of the impurities and comparison of the spectra and chromatographi c (HPLC and TLC) retention data of the isolated and synthesized materi als.