Bioanalysis of cimetidine by high-performance liquid chromatography

Cimetidine, N"-cyano-N-methyl-N'-[2[[(5-methyl-1H-imidazol-4-yl) methyl]-thio]ethyl]guanidine, is a specific histamine H2-receptor antagonist drug that is widely used in medicine to treat gastric ulcer disease and other pathological hypersecretory states. To study the bioavailability of cimetidine, it was necessary to develop a rapid and reliable high-performance liquid chromatography procedure for quantitating the drug in body fluids. In this new procedure, cimetidine is adsorbed directly from urine or plasma, without prior clean-up, on to a mini-column prepacked with C18 material (Sep-Pak C18 cartridge). Acetonitrile is used to elute the drug, and the eluate is analyzed by high-performance reversed-phase liquid chromatography on a Partisil 10 ODS column, with an aqueous phosphate-methanol mixture as the mobile phase and UV detection at 228 nm. This method for analyzing cimetidine in body fluids is rapid, accurate and precise and differs from previously reported methods in that it eliminates the need for performing bothersome single or multiple, dualphase solvent extractions. Moreover, slight modifications in the composition of the mobile phase permit the simultaneous determination of cimetidine metabolites.