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Process Related Impurities In Anti-Diabetic Drug Linagliptin

Sukumar Nandi, Akkina Naresh Gona Reddy, Paparaju Venkateswarlu A. Syam Prasad Reddy, K. Shantan Kumar Reddy

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Abstract


During the Linagliptin process development, several related substances in the range of 0.05% to 0.15% were observed by high performance liquid chromatography [HPLC] method. Liquid chromatography mass spectrometry [LC-MS] study was performed to identify the molecular mass of these impurities. The origin of these impurities was investigated. These impurities were synthetically prepared and characterized by IR, NMR and Mass analyzes. They were co-injected for their further confirmation. These impurities are 8-[(S)-3-Aminopiperidin-1-yl]-7-(but-2-ynyl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-1H-purine-2,6(3H,7H)-dione (Impurity-I), 7-(But-2-ynyl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-8-(piperidin-3-ylamino)-1H-purine-2,6(3H,7H)-dione (Impurity-II), 8-[(R)-3-Aminopiperidin-1-yl]-3-methyl-1,7-bis((4-methylquinazolin-2-yl)methyl)-1H-purine-2,6(3H,7H)-dione (Impurity-III), 8-[(R)-3-Aminopiperidin-1-yl]-1-(but-2-ynyl)-3-methyl-7-[(4-methylquinazolin-2-yl)methyl]-1H-purine-2,6(3H,7H)-dione (Impurity-IV), 1,7-Di(but-2-ynyl)-3-methyl-8-[(R)-3-(methyleneamino) piperidin -1-yl]-1H-purine-2,6(3H,7H)-dione (Impurity-V), 7-(But-2-ynyl)-8-(dimethylamino)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-1H-purine-2,6(3H,7H)-dione (Impurity-VI) and  8-[(R)-3-Aminopiperidin-1-yl]-7-[(E)-3-bromobut-2-enyl]-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-1H-purine-2,6(3H,7H)-dione (Impurity-VII).


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DOI: http://dx.doi.org/10.15520/jpro.2015.vol5.iss5.15

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