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
✍ Scribed by Saranjit Singh; Sanjeev Kumar; Nishi Sharda; Asit K. Chakraborti
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 104 KB
- Volume
- 91
- Category
- Article
- ISSN
- 0022-3549
- DOI
- 10.1002/jps.1176
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✦ Synopsis
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 a-carbon of intermediates 2 and 3 followed by elimination of the thiol moiety.