Karl Fischer (KF) Titration

This is a widely used analytical technique for determining water content in substances. It is especially important in the pharmaceutical, chemical, and food industries where moisture levels can impact product stability and quality.

Principle:

KF titration is based on the reaction of water with iodine and sulfur dioxide in the presence of an alcohol (usually methanol) and a base (like imidazole or pyridine). The reaction occurs in two steps.

Types of KF Titration :

1. Volumetric KF Titration:

    • Used for samples with water content above 0.1%.
    • A reagent containing iodine, SO₂, and a base in methanol is added to react with water.
    • The endpoint is detected electrochemically when excess iodine appears in solution.

    2. Coulometric KF Titration:

      • Used for samples with very low water content (<0.1%).
      • Iodine is generated electrochemically from an iodide-containing solution.
      • The amount of electricity used correlates directly to the water content.

      Applications in Pharmaceuticals

      • Determining moisture in API (Active Pharmaceutical Ingredients)
      • Checking water levels in excipients
      • Ensuring moisture control in finished dosage forms (tablets, injections, etc.)
      • Verifying compliance with pharmacopeial standards (USP, EP, JP, etc.)

      Advantages of KF Titration:

      • High accuracy & specificity for water.
      • Fast analysis (~1-5 minutes).
      • Suitable for solids, liquids, and gases.
      • Minimal interference compared to loss on drying (LOD).


      Related Topics:

      Partition CoefficientDissociation ConstantsBulk Density
      BioavailabilityBiotechnologyBioinformatics


      Resource Person: Susmita

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