Identification, Synthesis, and Characterization of Novel Impurities of Azilsartan Medoxomil, AT1 Receptor Antagonist

Abstract Azilsartan medoxomil is an angiotensin II type‐1 (AT1) receptor antagonist, often known as anangiotensin receptor blocker (ARB), which inhibits the renin–angiotensin–aldosterone system. During the laboratory‐scale synthesis of Azilsartan medoxomil, five distinct impurities were detected using high‐performance liquid chromatography (HPLC) and identified by liquid chromatography‐mass spectrometry (LC‐MS). Possible structures were proposed for these impurities and were designated as AZS Imp 1, AZS Imp 2, AZS Imp 3, AZS Imp 4, and AZS Imp 5. These impurities have been synthesized, and their structures were characterized using one and two‐dimensional −1 H NMR, −1 3 C NMR, mass spectrometry, and infrared spectroscopy, subsequently confirmed against the defined impurities. Identification, synthesis, and detailed characterization of five novel impurities in Azilsartan medoxomil improve understanding of the drug substance and finished product impurity profile. Unidentified or structurally uncharacterized impurities can harm patients; therefore, these discoveries are crucial for pharmaceutical quality, purity, and safety. Including these impurities in routine analytical monitoring will help meet regulatory criteria and build a long‐term medication safety control strategy. The synthesized impurities were employed as reference standards because of their potential significance, and a plausible explanation for the formation process of the five impurities was provided.