Efficient and Convenient Synthetic Routes for Sitagliptin Impurities

Abstract New efficient and convenient approaches have been devised for the synthesis of sitagliptin impurities. As a part of impurity profile study of an antidiabetic drug substance sitagliptin 1 , we encountered with six process related impurities. These impurities were detected by utilizing simple techniques such as high performance liquid chromatography (HPLC) and liquid chromatography ‐ mass spectrometry (LC–MS). All these impurities were synthesized and their presence in the sitagliptin sample was confirmed by co‐injection and matching the retention time with spiked impurities. The formation and control of these impurities during sitagliptin manufacture and synthesis of these impurities is discussed in detail. Synthesis of these impurities was accomplished by utilizing readily accessible starting materials, simple, convenient and concise reaction sequence.