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

2. 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

4. 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.”

5. 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

6. 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

8. 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.

9. 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

10. 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.

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

13. 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

14. 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.

15. 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

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