N-formyl derivatives of paroxetine

Abstract

A compound or composition comprising N-formyl paroxetine of formula (1) is useful as a pharmaceutical and as a synthetic intermediate. The N-formyl paroxetine can be an impurity in paroxetine substances and methods of assaying for such an impurity are also useful.

1 - 22 . (cancelled).  
     
     
         23 . A process for determining the stability or purity of a paroxetine substance or composition, which comprises assaying a paroxetine substance or composition for the presence of an N-formyl paroxetine compound of formula (1):  
       
         
           
           
               
               
           
         
       
     
     
         24 . The process according to  claim 23 , wherein said paroxetine substance or composition is a paroxetine pharmaceutical composition.  
     
     
         25 . The process according to  claim 24 , wherein said paroxetine pharmaceutical composition has been stored for at least three months before carrying out said assaying step.  
     
     
         26 . The process according to  claim 24 , wherein said assaying comprises the use of thin layer chromatography or high pressure liquid chromatography.  
     
     
         27 . A process, which comprises 
 forming a production lot of paroxetine pharmaceutical solid dosage forms wherein each dosage form comprises paroxetine or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient;    removing a sample of said paroxetine pharmaceutical solid dosage forms from said production lot;    assaying said sample for the presence and/or amount of N-formyl paroxetine; and    selling or releasing said production lot if said sample passes said assay with respect to the presence or amount of N-formyl paroxetine.    
     
     
         28 . The process according to  claim 27 , wherein said sample passes said assaying step if the amount of N-formyl paroxetine does not exceed a predetermined upper limit.  
     
     
         29 . The process according to  claim 28 , wherein said predetermined upper limit is the detection limit of said assaying step.  
     
     
         30 . The process according to  claim 27 , wherein said paroxetine or pharmaceutically acceptable salt is selected from the group consisting of paroxetine, paroxetine hydrochloride, paroxetine maleate, paroxetine acetate, and paroxetine methane sulfonate.  
     
     
         31 . The process according to  claim 28 , wherein said predetermined upper limit is 0.01% of N-formyl paroxetine based on the weight of the paroxetine compound.  
     
     
         32 . The process according to  claim 28 , wherein said predetermined upper limit is within the range of 0.01% to 0.1% of N-formyl paroxetine based on the weight of the paroxetine compound.  
     
     
         33 . The process according to  claim 28 , wherein said predetermined upper limit is 0.05% of N-formyl paroxetine based on the weight of the paroxetine compound.  
     
     
         34 . The process according to  claim 28 , wherein said predetermined upper limit is 0.1% of N-formyl paroxetine based on the weight of the paroxetine compound.  
     
     
         35 . The process according to  claim 28 , wherein said predetermined upper limit is 0.2% of N-formyl paroxetine based on the weight of the paroxetine compound.  
     
     
         36 . A process for manufacturing paroxetine hydrochloride tablets, which comprises 
 forming a production lot of at least 100,000 paroxetine pharmaceutical tablets, wherein said tablets comprise 1 to 50 mg of paroxetine hydrochloride and at least one pharmaceutically acceptable excipient;    removing a sample of said paroxetine hydrochloride tablets from said production lot;    testing said sample for compliance with a manufacturing specification, said testing including assaying said sample for the presence and/or amount of N-formyl paroxetine and said manufacturing specification including a predetermined upper limit for the amount of N-formyl paroxetine; and    selling or releasing said production lot if said sample meets said manufacturing specification.    
     
     
         37 . The process according to  claim 36 , wherein said predetermined upper limit for the amount of N-formyl paroxetine is the detection limit of said assaying.  
     
     
         38 . The process according to  claim 36 , wherein said predetermined upper limit for the amount of N-formyl paroxetine is within the range of 0.01% to 0.2% based on the weight of the paroxetine.  
     
     
         39 . The process according to  claim 38 , wherein said predetermined upper limit for the amount of N-formyl paroxetine is within the range of 0.01 % to 0.1% based on the weight of the paroxetine.  
     
     
         40 . The process according to  claim 36 , wherein said predetermined upper limit for the amount of N-formyl paroxetine is 0.1% based on the weight of the paroxetine.  
     
     
         41 . The process according to  claim 36 , wherein said forming of said production lot comprises blending paroxetine hydrochloride and at least one pharmaceutically acceptable excipient and compressing into said tablets.  
     
     
         42 . The process according to  claim 41 , wherein said predetermined upper limit for the amount of N-formyl paroxetine is within the range of 0.01% to 0.1% based on the weight of the paroxetine.  
     
     
         43 . The process according to  claim 36 , wherein said forming of said production lot comprises tabletting by direct compression.  
     
     
         44 . The process according to  claim 43 , wherein said predetermined upper limit for the amount of N-formyl paroxetine is within the range of 0.01% to 0.1% based on the weight of the paroxetine.