Control of impurities in diphenhydramine hydrochloride by an ion-pairing, reverse liquid chromatography method.

A precise, sensitive, repeatable and robust reverse-phase liquid chromatographic method has been developed for the control of seven possible impurities of diphenhydramine hydrochloride. The robustness of the method was examined by varying, in turn, each of four mobile-phase parameters (acetonitrile content, buffer salt concentration, ion-pair reagent concentration and pH). The method was linear in the range 0-0.14 mg mL(-1) for diphenhydramine hydrochloride with an acceptable precision and accuracy, and a limit of detection of 0.17 microg mL(-1). Five samples of diphenhydramine hydrochloride from two sources were analysed with the developed liquid chromatographic method.