Identification and Characterization of New Impurity in Phenoxybenzamine Hydrochloride Drug Substance

An unknown impurity was detected in the process of phenoxybenzamine hydrochloride drug substance at trace level by the high-performance liquid chromatography (HPLC) method during sample analysis. The impurity structure was predicted based on LC-MS analysis, a sample was synthesized and characterized. The proposed structure of the sample was confirmed by using NMR, FT-IR, LC-MS/MS, QTOF, and elemental analysis techniques. The structure corresponds to N-[(2-benzyloxy)ethyl]-N-(1-methyl-2-phenoxyethyl)benzylamine (PHB-1). The resulting impurity sample was co-injected in the HPLC system to confirm the peak retention time and relative retention times. A plausible mechanism for the generation and synthesis of PHB-1 was also discussed.