Identification, Synthesis, and Characterization of Unknown Impurity in the Famotidine Powder for Oral Suspension Due to Excipient Interaction by UPLC-MS/MS and NMR

摘要

Excipients interactions with the drug product are the most predominant causes for a product failure. Regulated guidelines have stringent limits for the unknown impurities observed in the pharmaceutical dosage forms. The quality of the excipients plays an important role in the finished product dosage forms which will form unknown impurities due to the impurities present in the excipients. Sometimes change in excipient manufacturer/lot gives not only the formulation related inconsistencies but hard-hitting encounters to analytical research due to their interactions with the drug product and formation of unknown impurities. Flavors used in the formulation process are the most possible origins to form impurities due to the trace level presence of aldehydes and ketones that were apparently used for its aroma. In this article identification, synthesis, and characterization of unknown impurity formed in the famotidine oral solution due to benzaldehyde which is present in the excipient of cherry flavor used in the formulation process. The samples of this impurity were investigated by HPLC and ultra performance liquid chromatography (UPLC)-MS/MS to generate the mechanism of the impurity formation. The impurity was synthesized, separated, and purified by preparative HPLC and characterized by UV, MS/MS, and NMR Results.