New findings on degradation of famotidine under basic conditions: identification of a hitherto unknown degradation product and the condition for obtaining the propionamide intermediate in pure form

Singh, Saranjit ; Kumar, Sanjeev ; Sharda, Nishi ; Chakraborti, Asit K. (2002) New findings on degradation of famotidine under basic conditions: identification of a hitherto unknown degradation product and the condition for obtaining the propionamide intermediate in pure form Journal of Pharmaceutical Sciences, 91 (1). pp. 253-257. ISSN 0022-3549

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Official URL: http://jpharmsci.org/article/S0022-3549(16)30875-9...

Related URL: http://dx.doi.org/10.1002/jps.1176

Abstract

The degradation behavior of famotidine (1) was investigated in 25% ammonia solution and in 2 M NaOH. The hydrolysis of the drug in ammonia resulted in separation of [3-[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionamide (3), an impurity listed in British Pharmacopoeia. The treatment with 2 M NaOH resulted in formation of [3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionyl]sulfamide (2) and 3. These products further decomposed to [3-[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propionic acid (4) and a heretofore unknown product, 5. The latter separated out in the reaction mixture as brown shiny crystals. Proton and carbon-13 nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis of the charcoal-treated product established the structure. The formation of 5 is postulated to involve abstraction of a proton from the alpha-carbon of intermediates 2 and 3 followed by elimination of the thiol moiety.

Item Type:Article
Source:Copyright of this article belongs to Elsevier.
Keywords:Famotidine; Degradation; Basic Conditions, BP Impurity, Unknown Product
ID Code:101052
Deposited On:19 Jan 2017 07:24
Last Modified:19 Jan 2017 07:24

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