Mycophenolate mofetil impurity

Abstract

Provided is an impurity of mycophenolate mofetil, processes for its preparation and its use as a reference.

1 . A process for the isolation of Compound 1 having the formula: 
       
         
           
           
               
               
           
         
         from a mixture comprising mycophenolate mofetil and Compound 1 comprising: 
         a) providing a solution comprising mycophenolate mofetil and Compound 1 in a solvent; 
         b) washing the solution with an aqueous acidic solution to obtain a two-phase system; 
         c) separating the organic phase containing mycophenolate mofetil from the aqueous acidic phase; 
         d) adding an aqueous basic solution to the aqueous acidic phase; and 
         e) recovering Compound 1. 
       
     
     
         2 . The process of  claim 1 , wherein the solvent in step a) is selected from the group comprising: alkyl acetates, chlorinated hydrocarbons and aromatic hydrocarbons. 
     
     
         3 . The process of  claim 1 , wherein said solvent is isobutyl acetate. 
     
     
         4 . The process of  claim 1 , wherein the aqueous acid solution in step b) contains either a mineral acid or an organic acid. 
     
     
         5 . The process of  claim 4 , wherein said aqueous acid solution contains any one of hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid and trifluoromethanesulfonic acid. 
     
     
         6 . The process of  claim 5 , wherein said aqueous acid solution contains acetic acid. 
     
     
         7 . The process of  claim 1 , the aqueous basic solution added in step d) contains either an inorganic or organic base. 
     
     
         8 . The process of  claim 7 , wherein said aqueous basic solution contains sodium bicarbonate. 
     
     
         9 . Mycophenolate mofetil having an amount of Compound 1 having the formula: 
       
         
           
           
               
               
           
         
         of about 0.01 to about 0.1% area by HPLC. 
       
     
     
         10 . An HPLC method for quantifying the amount of Compound 1 having the formula: 
       
         
           
           
               
               
           
         
         in mycophenolate mofetil comprising the steps of: 
         a) preparing a sample solution of the mycophenolate mofetil sample in acetonitrile; 
         b) injecting the sample solution onto an about 250.0 mm×4.6 mm, 5 μm C8 HPLC column; 
         c) gradient eluting the sample with a mixture of acetonitrile and water, adding triethylamine and adjusting the pH to about 6 with diluted phosphoric acid (A Eluent) and a B Eluent with a buffer: acetonitrile ratio of about 15:85, according to the following profile: 
       
       
         
           
                 
               
                     
                 
                   HPLC Gradient 
                 
                 
                 
                 
                 
                 
               
                     
                   Flow rate 
                   Time 
                     
                     
                 
                     
                   [mL/min] 
                   (min) 
                   A Fluent (V/V %) 
                   B Eluent (V/V %) 
                 
                     
                     
                 
                 
                 
                 
                 
                 
               
                     
                   1.5 
                   0 
                   100 
                   0 
                 
                     
                   1.5 
                   15 
                   100 
                   0 
                 
                     
                   1.5 
                   37 
                   28 
                   72 
                 
                     
                   1.5 
                   37.1 
                   100 
                   0 
                 
                     
                   1.5 
                   40 
                   100 
                   0 
                 
                     
                     
                 
             
                
                
               
            
             
                
                
                
               
            
             
                
                
                
                
                
                
               
            
           
         
         d) measuring of the amounts of each impurity at about 250 nm wavelength with a UV detector. 
       
     
     
         11 . A method for analyzing a sample of mycophenolate mofetil comprising the steps of:
 a) performing chromatography on the sample to obtain data; and   b) comparing the data with the chromatography data of Compound 1 having the formula:   
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 11 , wherein the method comprises the following steps:
 (a) preparing a solution of mycophenolate mofetil containing Compound 1;   (b) subjecting the solution to a high pressure liquid chromatography to obtain a chromatogram; and   (c) comparing a peak obtained in the chromatogram to a peak resulting from the Compound 1.   
     
     
         13 . The method of  claim 11 , wherein the method comprises the following steps:
 (a) preparing a solution of mycophenolate mofetil containing Compound 1;   (b) subjecting the solution to thin layer chromatography to obtain a chromatogram; and   (c) comparing a band or spot obtained in the chromatogram to a peak or band resulting from the degradation product.   
     
     
         14 . An HPLC method of assaying mycophenolate mofetil comprising the steps of:
 a) preparing a sample solution of the mycophenolate mofetil in acetonitrile;   b) injecting the sample solution onto an HPLC column;   c) eluting the sample with a mixture of acetonitrile and water;   d) adding triethylamine, and adjusting the pH to about 6; and   e) measuring of the amounts of each impurity with a detector and appropriate recording device.