Pharmaceutical Chemistry
Phase 4 – Purity Assessment & Analytical Validation
Karl Fischer Titration

Karl Fischer Titration

Karl Fischer titration provides highly precise, specific quantification of water content within a sample, exploiting a stoichiometric chemical reaction...

Pharmaceutical ChemistryPhase 4 – Purity Assessment & Analytical Validation1 min readUpdated 2026-07-13

Karl Fischer titration provides highly precise, specific quantification of water content within a sample, exploiting a stoichiometric chemical reaction between water and an iodine-sulphur dioxide reagent system that occurs with high selectivity even in the presence of other volatile or reactive sample components. Karl Fischer titration is of particular pharmaceutical importance because residual moisture content directly affects compound stability during storage (promoting hydrolytic degradation and microbial growth) and can materially affect the accuracy of potency assays that assume an anhydrous, or precisely defined hydrate-form, reference weight; volumetric Karl Fischer titration is typically applied to samples containing above approximately 0.1% water, while the more sensitive coulometric variant is applied to trace-level moisture determination in samples expected to contain very low water content.

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