GYANDEEP ACADEMY 
                        Mr. Arun Patidar (M.Pharm) Mob: 9826672215, 9644067667, 34 Prakash Nagar Navlakha, Indore 
                                              Download study material (Notes) www.gyandeepacademy.in 
                        Key Notes: Pharmaceutical Inorganic Chemistry (BP104T) B Pharm I SEM 
          
         UNIT – I IMPURITIES IN PHARMACEUTICAL SUBSTANCES 
         Impurity-Any undesirable substance present in drug which affect safety, efficacy, stability or 
         physical characteristics of drug.  
         Types of Impurities-  
                  Inorganic 
                  Organic 
                  Residual solvents  
                  filter aid 
         Sources of impurities in Pharmaceutical Substances: 
              -   Raw Material- ZnO + H2SO4 → ZnSO4 + H2O   (ZnO contain Al, Cu, Mg, Ni, As, 
                  Fe as impurities) 
              -   Starting material as impurities- due to incompleteness of reaction, imperfect mixing 
                  2Zn + O2  → 2 ZnO (Zinc metal may be present in final product) 
              -   Intermediate product as impurities- (KIO may be present in final product) 
                                                                              3 
                  6KOH + 3I    → 5KI + KIO + 3H2O 
                                  2                      3
                  KIO  + 3C  → KI + 3CO 
                        3
              -   Reagents and Catalyst used in Manufacturing process- if not completely removed 
                  by washing, these may be present in final product. 
              -   Improper selection  of  reaction  vessels-  metallic  such  as  copper,  iron,  cast  iron, 
                  galvanized iron, silver, aluminium, nickel, zinc and lead. 
              -   Improper  selection  of  container-Reaction  with  container  material,  leaching  of 
                  material from plastic, rubber and metal container. 
              -   Atmospheric  Contamination-  Atmosphere  may  containdust  (aluminium  oxide, 
                  sulphur, silica, soot etc.) and some gases like carbon dioxide, sulphur dioxide, arsine 
                  and hydrogen sulphide. 
              -   Faulty (Improper) storage condition- undesirable decomposition due to oxidation, 
                  hydrolysis, reduction or photoreaction. 
          
          
         Emergency Regarding Blood Donner Please Contact – 9826672215, 9644067667                                                Page 1 
          
                                                      GYANDEEP ACADEMY 
                         Mr. Arun Patidar (M.Pharm) Mob: 9826672215, 9644067667, 34 Prakash Nagar Navlakha, Indore 
                                                Download study material (Notes) www.gyandeepacademy.in 
                         Key Notes: Pharmaceutical Inorganic Chemistry (BP104T) B Pharm I SEM 
           
                Limit Tests- Quantitative or semi-quantitative tests designed to identify and control 
                   small quantities of impurity which are likely to be present in the substances. 
                    
                                                          
                   Limit Test for Chloride-  
                   Principle : It is based upon the chemical reaction between silver nitrate and soluble chlorides in 
                   presence of dilute nitric acid to give opalescence of silver chloride. If the Opalescence produced is 
                   compared with the standard solution. If the opalescence in the sample is less than the standard, it passes 
                   the test. If it is more than the standard, it fails the test. 
                                               HNO3(10ml Dil.) 
                    (Sample) Cl- + AgNO    →                     AgCl + NO - 
                                                    3                             3
                            Silver Nitrate (1ml of 0.1M)                   Siver Chloride (Turbidty) 
              Test solution-dissolve Specified quantity of sample in water or prepare a solution as 
                 directed in the individual monograph → Transfer in nessler cylinder → add 10ml dilute 
                 HNO3 → add water upto 50ml →add 1ml of 0.1M AgNO3 solution →stir immediately 
                 → allow to stand for 5 min.→ compare turbidity with standard solution. 
              Standard solution- 10ml of Chloride standard solution (25ppm Cl-) treated in  same 
                 manner. 
              HNO3 prevent precipitation of other impurities. 
                                                                                                                                                      
           
           
          Emergency Regarding Blood Donner Please Contact – 9826672215, 9644067667                                                      Page 2 
           
                                GYANDEEP ACADEMY 
               Mr. Arun Patidar (M.Pharm) Mob: 9826672215, 9644067667, 34 Prakash Nagar Navlakha, Indore 
                             Download study material (Notes) www.gyandeepacademy.in 
               Key Notes: Pharmaceutical Inorganic Chemistry (BP104T) B Pharm I SEM 
       
                                   
            Limit Test for Sulphate- 
         Principle : It is based upon the chemical reaction between Barium chloride and soluble sulphate in presence of 
         dilute Hydrochloric acid . The turbidity produced is compared with the standard solution. Barium sulphate reagent 
         contains barium chloride, sulphate – free alcohol and small quantity of potassium sulphate. The inclusion of the 
         small quantity of potassium sulphate in the reagent increase the sensitivity of the test. Alcohol prevents super 
         saturation and more uniform turbidity develops. If the turbidity produced in the test is more intense than the standard 
         turbidity it fails the test . otherwise, it passes the test. 
             
                                                 
                                  0.15ml Acetic acid
                             --                       - 
                 (Sample) SO  + BaCl    → BaSO4 + 2Cl
                            4        2 
            1ml of 25% BaCl2, Barium sulphate Reagent  (1.5ml )     Barium Sulphate(Turbidty) 
             
      Barium sulphate Reagent-15ml of 0.5%BaCl2+20ml Alcohol+5ml of 0.0181%K2SO4+water 
      upto 100ml. 
      Standard solution- 15 ml of sulphate standard solution (10 ppm SO4 ) treated in same manner. 
         Acetic Acid prevent precipitation of other impurities. 
                                                                                           
          
      Emergency Regarding Blood Donner Please Contact – 9826672215, 9644067667    Page 3 
       
                                                                                            GYANDEEP ACADEMY 
                                           Mr. Arun Patidar (M.Pharm) Mob: 9826672215, 9644067667, 34 Prakash Nagar Navlakha, Indore 
                                                                                   Download study material (Notes) www.gyandeepacademy.in 
                                           Key Notes: Pharmaceutical Inorganic Chemistry (BP104T) B Pharm I SEM 
                  
                              Limit Test for Iron-  
                                                                                        
                 Principle : The test depends upon the reaction between ferrous iron and thioglycollic acid in the presence of 
                 ammonia When a pale pink to deep reddish purple colour is produced. Ferric iron is reduced to ferrous iron 
                 by the thioglycollic acid and the compound produced is ferrous thioglycollate . Citric acid forms a soluble 
                 complex with iron and prevents its precipitation by ammonia as ferrous hydroxide. Ferrous thioglycollate is 
                 colourless in neutral or acid solutions. The colour develops only in the presence of alkali. It is stable in the 
                 absence of air but fades when exposed to air due to oxidation to the ferric compound. Therefore the colours 
                 should be compared immediately after the time allowed for full development of colours is over. 
                                                                                  
                                                                                  Citric acid (2ml of 20%), Ammonia to make alkaline 
                                                                 ++                                                                                                   -                   + 
                                  (Sample) Fe  + 2 HSCH COOH → Fe(HSCH COO)  + 2H
                                                                                                 2                                                     2                  2
                                                                ThioglycollicAcid(0.1ml)                         ferrous thioglycollate (Purple) 
                         Standard solution- 2ml of Iron standard solution (20ppm Fe) treated in same manner. 
                                                                                                                                                                                                                                                                   
                          
                 Emergency Regarding Blood Donner Please Contact – 9826672215, 9644067667                                                                                                                                                   Page 4