IMPURITY OF FAMOTIDINE
The present invention is directed to a new impurity of famotidine, process for preparing and isolating it. The invention is further related to analytical methods of its identification, synthesis and characterization.
1 . A compound of Formula I or its salts or enantiomers
2 . The compound of claim 1 , characterized by a chemical purity of more than 50%.
3 . The compound of claim 1 , wherein the compound of Formula I is in the presence of famotidine or a pharmaceutically acceptable salt thereof and the compound of Formula I is present in an amount of less than 0.5% by mole.
4 . The compound of claim 1 , wherein the compound of Formula I is present in a pharmaceutical composition comprising a therapeutically effective amount of famotidine or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is present in an amount less than 0.5% by weight of famotidine.
5 . The compound of claim 4 , wherein the pharmaceutical composition is substantially free of the compound of Formula I.
6 . The compound of claim 4 , wherein the composition comprising the compound of Formula I is an oral composition.
7 . The compound of claim 1 , characterized by a HPLC chromatogram having a peak at 57 min and 2.3 RRT.
8 . The compound of claim 1 , characterized by having 1 H NMR spectrum with a pair of doublets at 7.8 ppm.
9 . The compound of claim 1 , characterized by having 1 H NMR spectrum with a singlet peak at 9-10 ppm.
10 . The compound of claim 1 , characterized by having 1 H NMR spectrum with a peak at 9.45 ppm.
11 . The compound of claim 1 , characterized by absence of 1 H NMR spectrum with a peak at 8.4 ppm.
12 . The compound of claim 1 , characterized by having 1 H NMR spectrum with peaks at about 2.4 to 2.8, 3.68, 5.64 to 5.68, 6.254, 6.83, 7.2 to 7.8 and 9.45 ppm.
13 . The compound of claim 1 , characterized by mass spectroscopy in negative ion mode having m/z value of about 236 in product ion mode.
14 . The compound of claim 1 , characterized by mass spectroscopy in negative ion mode with absence of m/z value of about 147 and 95 in product ion mode.
15 . The compound of claim 1 , characterized by mass spectroscopy in negative ion mode having m/z value of about 187, 236 and 424 in product ion mode.
16 . The compound of claim 1 , characterized by mass spectroscopy in positive ion mode having m/z value of about 106, 155, 189, 238 and in product ion mode.
17 . The compound of claim 1 , characterized by mass spectroscopy in positive ion mode with absence of m/z value of about 259 in product ion mode.
18 . A process for the preparation of the compound of Formula I comprising: contacting famotidine with benzaldehyde to form the compound of Formula I; and isolating the compound of Formula I.
19 . A method of testing the purity of a sample of famotidine or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising famotidine, wherein the method comprises assaying the sample for the presence of the compound of Formula I of claim 1 .
20 . A method of reducing the level of the compound of Formula I of claim 1 in a pharmaceutical composition comprising famotidine or salt thereof, the method comprising formulating the pharmaceutical composition using one or more pharmaceutical excipients containing a substantially low amount of benzaldehyde or being devoid of benzaldehyde.