Some samples do not easily release water for Karl Fischer determinations. So, what are the workable options in such instances? This article from Issue 12 of the Analytix Reporter, produced by Merck, discusses the steps that can be taken to release water from such samples to achieve a reliable and accurate water content determination.


Karl Fischer titration for water determination is probably the best known and most widely used titration method. The reaction mechanism is well explored and there is a broad offering of suitable reagents and instruments to be used. The method is described in numerous regulations and guidelines with thousands of available applications. As part of method development, the type of sample should be considered. Specifically, how to best release water from it so as to make it completely accessible for titration.

The Karl Fischer method determines only water and no other compounds because of the selective and stoichiometric reaction between the water in the sample and the iodine in the reagent. There are multiple different ways to release the water from the samples and determine the correct water content. The following preconditions and questions are important to consider before getting started:

  • The water in the sample needs to be completely released. What is the best solvent or method to do this?
  • Any contamination with ambient moisture must be avoided. Is the sample hygroscopic? Is the instrument tight? With hygroscopic samples fast working procedures are needed and the samples have to be kept protected in closed containers.
  • Water or iodine generating and consuming side reactions need to be suppressed or avoided. Is the sample reacting with the components in the Karl Fischer reagents and how can this be prevented?

This article addresses how water is present in a sample and how to completely release it, methods to dissolve or extract the water from the samples, solubilizers to dissolve the sample in the Karl Fischer solvent, internal extraction/dissolution, and external extraction/dissolution. In addition a convenient method that can be used for critical samples that are not soluble, cause side reactions, or are solid with low water content using the Karl Fischer oven in combination with a volumetric or coulometric titrator is explained.

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*The life science business of Merck operates as MilliporeSigma in the U.S. and Canada.

Published  Jun 23, 2022

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