Karl Fischer Titration This ppt is for educational purpose K. G. Baheti Y. B. Chavan College of Pharmacy Aurangabad

What is Karl Fischer titration? • Karl Fischer is an analytical technique used to measure the moisture (water) content in solids, liquids or gases. • Karl Fischer was a chemist working at a petrochemical company in Germany in the 1930’s. He developed the technique. Composition : Iodine, SO2 , Pyridine and methoanol

How does K-F titration work? In general, K-F titration can be summarized into a series of steps: 1. Add reagent (“titrant”) to a burette. The reagents include alcohol, SO2, a base and I2 2. Add sample solvent to the titration vessel and stirr 3. Zero the instrument by titrating unwanted moisture in the system 4. Add the weighed sample to the titration vessel 5. Begin adding reagent from the burette while stirring 6. When the endpoint is reached, the electrode will detect no change in current upon addition of more reagent 7. By knowing how much titrant was added, the water content can be calculated 8. Normally, the K-F instrument does the calculations and reports the results as “% water” or “ppm water.”

Theory/principle of Karl Fischer titration The Bunsen reaction is a chemical reaction that describes water, sulfur dioxide, and iodine reacting to form sulfuric acid and hydrogen iodide. One mole of iodine disappear against each mole of water present in the sample

Advantages of Karl Fischer Titration High accuracy and precision Selectivity for water Small sample quantity Easy sample preparation Short time of analysis Large measuring range Used for all forms of samples Suitability for automation Independence of presence of other volatile substance

Karl Fischer Reagent Preparation All the reagent should be free from moisture. 400ml of methanol (water content less than 0.03%) in a stopper flask of 750ml capacity and then add 80gms of pyridine and mix it. Immerged the flask in freezing mixture and pass slowly the SO2 gas into the cold mixture with stirring till the weight increases by 20gm. Then add 45gm of iodine and shake well to dissolve. Allow the mixture to stand for 2 hours before use. Store in moisture free atmosphere and protect from light.

Stability of Karl Fischer reagent Karl Fischer reagent is equivalent to 3.5 mg /ml water The concentration KF reagent is decreases upon passage of time. Hence following precaution should be taken :- One or two day before prepare the reagent Prevent the contamination of sample or reagent by atmospheric moisture Dried glassware Storage of solution in air tight bottle Minimize the contact of solution and reagent with air during titration

Standardization of Karlfisher reagent : Sodium tartrate dihydrate is a primary standard for KF reagent standardization. It contains 15.6%water. 1. Weigh appx.100mg of the sodium tartrate dihydrate crystals and transfer carefully into the titration vessel containing methanol. 2. Close the sample hole with rubber lid and stir the solution for 2minutes. Note down the burette reading. 3. Press” START” button and start the titration. It takes 2 to 3 mins to complete the titration which depends on the moisture content of the sample. 4. On display of “END” lamp take the burette reading.   Calculation of KF factor (F) = M * O.1566 (mg/ml) / V   Where M=Weight of the sodium tartrate dihydrate V=Volume of the K.F reagent added.   The range of K.F. factor for most of the solutions ranges from 4 to 5. Procedure for sample : Add unknown sample of definite quantity into the titration vessel and carry on the titration. Note the end point volume of the K.F reagent. Percent of moisture content of sample (M.C.) = K.F. Volume in ml*F*100 / Weight of sample in mg Standardization can also be done with water methanol mixture.

Dead stop end point assembly Current will not flow due to polarizing substance, current shall get polarized only when the electrode gets depolarized.

End point detection By electrometric technique using dead stop end point method. End point is achieved, when the pointer of the manometer gets deflected for 10 to 15 seconds due to the iodine present in the reagent

Determination of water in Prednisolone sod. Phosphate Requirement : KFR 100ml, Prednisolone sodium phosphate 0.2gms, anhydrous methanol 20ml Method: in the titration vessel add 20ml of anhydrous methanol and titrate to atmospheric end point with KFR. Then add 02.gm of drug sample and titrate with KFR to atmospheric end point . Difference between two titrations give volume (v) of KFR consumed by drug. Minimum water equivalent is 3.5mg of water per ml of KFR. Hence, the % of water w/w is given by formula:- Water % (w/w) = (v X 3.5 /wt of sample in mg ) X 100 Precautions: KFR and solution should be anhydrous Necessary care should be taken to prevent atm moisture exposure KFR should be protected from light KFR should be preferably store in a bottle fitted with an automatic burette Water equivalent of KFR should always be determined before use.

Prescribed limit of water %w/w Applications Name of drug Prescribed qty Prescribed limit of water %w/w Rifamycine sodium 0.2gm 12 to 17 Sodium Methyl hydroxy benzoate 1.0gm NMT 5.0 Triamcinolone acetonide NMT 2.0

Applications Application in the following industries Plastic Oil Fats Wood Cotton Paper Explosives Leather Textile Pharmaceuticals Agriculture