Pure darifenacin hydrobromide substantially free of oxidized darifenacin and salts thereof and processes for the preparation thereof

Abstract

Provided are darifenacin hydrobromide free of oxidized darifenacin, and processes for the preparation thereof.

1 . An HPLC method for determining the presence and level of oxidized darifenacin and salts thereof in a darifenacin hydrobromide sample comprising: (a) combining a darifenacin hydrobromide sample with a mixture of acetonitrile:water in a ratio of about 1:1, to obtain a solution; (b) injecting the solution into a 150×4.6 mm×5.0 μm Phenyl C6 column; (c) eluting the sample from the column using a mixture of acetonitrile:water in a ratio of 9:1 and buffer as an eluent; and (d) measuring the oxidized darifenacin content in the sample with a UV detector. 
   
   
       2 . A process of determining the presence of a compound of the following formula I 
     
       
         
         
             
             
         
       
     
     in a sample comprising the compound of formula I and a compound of the following formula II 
     
       
         
         
             
             
         
       
     
     by a process comprising carrying out HPLC or TLC with the compound of formula I as a reference marker, wherein Y is a leaving group selected from the group consisting of Cl, I, brosyl, mesyl, tosyl, trifluoroacetyl, and trifluoromethansulfonyl. 
   
   
       3 . The process of  claim 2 , comprising: (a) measuring by HPLC or TLC the relative retention time corresponding to the compound of formula I in a reference marker sample; (b) determining by HPLC or TLC the relative retention time corresponding to the compound of formula I in a sample comprising a compound of formula I and a compound of formula II; and (c) determining the relative retention time of the compound of formula I in the sample by comparing the relative retention time of step (a) to the relative retention time of step (b). 
   
   
       4 . The process of  claim 3 , wherein Y is Cl. 
   
   
       5 . A process of determining the amount of a compound of the following formula I 
     
       
         
         
             
             
         
       
       in a sample comprising the compound of formula I and a compound of the following formula II 
     
     
       
         
         
             
             
         
       
       by a process comprising carrying out an HPLC with the compound of formula I as a reference standard, wherein Y is a leaving group selected from the group consisting of Cl, I, brosyl, mesyl, tosyl, trifluoroacetyl, and trifluoromethansulfonyl. 
     
   
   
       6 . The process of  claim 5 , comprising: (a) measuring by HPLC the area under a peak corresponding to a compound of formula I in a reference standard comprising a known amount of the compound of formula I; (b) measuring by HPLC the area under a peak corresponding to a compound of formula I in a sample comprising a compound of formula I and a compound of formula II; and (c) determining the amount of the compound of formula I in the sample by comparing the area of step (a) to the area of step (b). 
   
   
       7 . The process of  claim 6 , wherein Y is Cl. 
   
   
       8 . The HPLC method of  claim 3 , comprising: (a) combining a sample of the compound of formula I with a mixture of acetonitrile:water in a ration of about 1:1, to obtain a solution; (b) injecting the solution into a 250×4.6 mm×0.5 μm C18 column; (c) eluting the sample from the column using a mixture of acetonitrile and buffer as an eluent; and (d) measuring the amount of the compound of formula I in the sample with a UV detector at a wavelength of 215 nm. 
   
   
       9 . the method of  claim 8 , wherein Y is Cl. 
   
   
       10 . The HPLC method of  claim 6 , comprising: (a) combining a sample of the compound of formula I with a mixture of acetonitrile:water in a ratio of about 1:1, to obtain a solution; (b) injecting the solution into a 250×4.6 mm×0.5 μm C18 column; (c) eluting the sample from the column using a mixture of acetonitrile and buffer as an eluent; and (d) measuring the amount of the compound of formula I in the sample with a UV detector at a wavelength of 215 nm. 
   
   
       11 . The method of  claim 10 , wherein Y is Cl.