This article describes about Karl Fischer Titrations, Principle, Different types, Applications, Instrumentations, advantages and limitations.

What is mean by Karl Fischer Titrations ?

It is a well-established method for determining the water content in Drug product and Drug substances. This method is based on a chemical reaction between Sulphur dioxide, Iodine and water in presence of pyridine and solvent (Methanol). It is Redox type of titrations. (Oxidation & Reduction both takes place).

History of Karl Fischer Titrations

The Karl Fischer titration method was first introduced by a German chemist named Karl Fischer in 1935. He developed this method as a more accurate and reliable way to measure the water content of samples.

Principles of Karl Fischer Titrations

Karl Fischer titration is based on a chemical reaction between Sulphur dioxide, iodine and water in presence of pyridine & solvent (Methanol)

The reaction is carried out in a titration cell containing a solvent, a titrant, and a sample of the substance being analyzed.

The titrant is a solution of iodine in a solvent that contains sulfur dioxide and a base. The base serves to neutralize any acid that may be present in the sample, while sulfur dioxide helps to reduce the iodine to iodide. The reaction between iodine and water is highly exothermic, so the temperature of the reaction mixture is closely monitored to ensure accurate results.

Types of Karl Fischer Titrations

There are mainly Two Main types of Karl Fischer Titrations:

Volumetric Titrations :

These titrations are used for samples that contain a relatively high water content. Volumetric titrations involve the addition of a known amount of titrant to the sample until the end point is reached moreover end point detection through potentiometric technique.

Coulometric Titrations:

These titration method is used for samples with low water content. The method contains electrochemical production of iodine within the titration cell by passing an electric current through an electrode moreover end point detection through electrochemical Technique

Applications of Karl Fischer Titrations

this techniques are used to determine the water content of drug product and drug substances. Moreover it can detect water content present in Solid, Liquid and Gas.

Instrumentation for Karl Fischer Titrations

It require specialized equipment that includes below components

Titration cell : It is designed to allow the titrant to be added to the sample while the reaction mixture is stirred continuously

Burette : Burette is used to dispense the titrant into the titration cell

Stirrer : Stirrer ensures that the reaction mixture is well mixed

Coulometer : Coulometer is used in Coulometric Titrations to generate Iodine within the titrations.

Advantages of Karl Fischer Titrations

First and foremost advantages of Karl Fischer Titration is  they are highly accurate and reliable, with detection limits as low as 1 ppm furthermore They are relatively fast and easy to perform, requiring only a small amount of sample and no sample preparation.

These titrations are highly accurate and reliable, but there are some limitations to this method as one major limitation is, it only measures water content of a sample, and it cannot distinguish between different forms of water, such as bound water and free water. Additionally, the presence of other interfering substances in the sample, such as solvents or surfactants, can affect the accuracy of the results.

What is mean by “drift in Karl Fischer Titrations”?

To detect the Atmospheric moisture before start of analysis (Atmospheric Moisture should be zero while Testing.)