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Identification and Synthesis of Impurities Formed During Preparation of Azelnidipine
Corresponding Author(s) : K. Sudarshan Rao
Asian Journal of Chemistry,
Vol. 26 No. 15 (2014): Vol 26 Issue 15
Abstract
Azelnidipine (1), dihydropyridine-based calcium antagonists (DHPs) are one of the widely used drugs for treatment of hypertension. During the laboratory optimization and later during its bulk synthesis the formation of various impurities was observed. The impurities formed were monitored and their structures were tentatively assigned on the basis of their fragmentation patterns in LC-MS. Most of the impurities were synthesized and their assigned constitutions confirmed by co-injection in HPLC. We describe herein the formation, synthesis and characterization of these impurities. Our study will be of immense help to others to obtain chemically high pure azelnidipine.
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- P. Cozzi, G. Carganico, D. Fusar, M. Grossoni, M. Menichincheri, V. Pinciroli, R. Tonani, F. Vaghi and P. Salvati, J. Med. Chem., 36, 2964 (1993); doi:10.1021/jm00072a017.
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- T. Ogawa, A. Nakazato, K. Tsuchida and K. Hatayama, Chem. Pharm. Bull. (Tokyo), 41, 108 (1993); doi:10.1248/cpb.41.108.
- K. Meguro, M. Aizawa, T. Sohda, Y. Kawamatsu and A. Nagaoka, Chem. Pharm. Bull. (Tokyo), 33, 3787 (1985); doi:10.1248/cpb.33.3787.
- I. Morita, Y. Haruta, T. Tomita, M. Tsuda, K. Kandori, M. Kise and K. Kimura, Chem. Pharm. Bull. (Tokyo), 35, 4819 (1987); doi:10.1248/cpb.35.4819.
- G. Jones, in eds.: R. Adams, A.H. Blatt, V. Boekelheide, T.L. Cairns, D.J. Cram and H.O. House, Organic Reactions: The Knoevenagel Conden-sation, John Wiley & Sons, Inc., New York, Vol. 15, p. 204 (1967).
- M. Iwanami, T. Shibanuma, M. Fujimoto, R. Kawai, K. Tamazawa, T. Takenaka, K. Takahashi and M. Murakami, Chem. Pharm. Bull. (Tokyo), 27, 1426 (1979); doi:10.1248/cpb.27.1426.
- A.B. Boese Jr., Ind. Eng. Chem., 32, 16 (1940); doi:10.1021/ie50361a004.
- ICH guidelines, Q3A (R): Impurities in New Drug Products: The Quality Guidelines for Active Pharmaceutical Ingredients Related To Impurities According to the International Conference of Harmonization (2002); http://www.ich.org.
References
P. Cozzi, G. Carganico, D. Fusar, M. Grossoni, M. Menichincheri, V. Pinciroli, R. Tonani, F. Vaghi and P. Salvati, J. Med. Chem., 36, 2964 (1993); doi:10.1021/jm00072a017.
J.L. Archibald, G. Bradley, A. Opalko, T.J. Ward, J.C. White, C. Ennis and N.B. Shepperson, J. Med. Chem., 33, 646 (1990); doi:10.1021/jm00164a028.
G. Marciniak, A. Delgado, G. Leclerc, J. Velly, N. Decker and J. Schwartz, J. Med. Chem., 32, 1402 (1989); doi:10.1021/jm00126a042.
T. Ogawa, A. Nakazato, K. Tsuchida and K. Hatayama, Chem. Pharm. Bull. (Tokyo), 41, 108 (1993); doi:10.1248/cpb.41.108.
K. Meguro, M. Aizawa, T. Sohda, Y. Kawamatsu and A. Nagaoka, Chem. Pharm. Bull. (Tokyo), 33, 3787 (1985); doi:10.1248/cpb.33.3787.
I. Morita, Y. Haruta, T. Tomita, M. Tsuda, K. Kandori, M. Kise and K. Kimura, Chem. Pharm. Bull. (Tokyo), 35, 4819 (1987); doi:10.1248/cpb.35.4819.
G. Jones, in eds.: R. Adams, A.H. Blatt, V. Boekelheide, T.L. Cairns, D.J. Cram and H.O. House, Organic Reactions: The Knoevenagel Conden-sation, John Wiley & Sons, Inc., New York, Vol. 15, p. 204 (1967).
M. Iwanami, T. Shibanuma, M. Fujimoto, R. Kawai, K. Tamazawa, T. Takenaka, K. Takahashi and M. Murakami, Chem. Pharm. Bull. (Tokyo), 27, 1426 (1979); doi:10.1248/cpb.27.1426.
A.B. Boese Jr., Ind. Eng. Chem., 32, 16 (1940); doi:10.1021/ie50361a004.
ICH guidelines, Q3A (R): Impurities in New Drug Products: The Quality Guidelines for Active Pharmaceutical Ingredients Related To Impurities According to the International Conference of Harmonization (2002); http://www.ich.org.