Identification and characterization of potential impurities of valsartan, AT1 receptor antagonist

Five impurities (related substances) were detected during the impurity profile study of an antihypertensive drug substance, valsartan. A simple gradient high performance liquid chromatographic method (HPLC) and liquid chromatography–mass spectrometry (LC–MS) were used for the detection. Based on the spectral data (IR, NMR and MS) followed by synthesis, these impurities were characterized as (S)-N-(1-carboxy-2-methylprop-1-yl)-N-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity I); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-(5-phenylthio)pentanoyl-N-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity II); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-(5-phenyl)pentanoyl-N-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity III); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-4-pentenoyl-N-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity IV); (S)-N-(1-carboxy-2-methylprop-1-yl)-N-(5-hydroxy)pentanoyl-N-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]amine (impurity V).