Determining water content is a CMC requirement for pharmaceuticals and Karl Fischer titration is the most common way to determine water content within for most drug products. Karl Fischer moisture analysis can be conducted on solids, liquids and even gasses. For most solids, the product should be dissolved in methanol first. Liquids can usually be injected right into the instrument and gasses can be analyzed with Karl Fischer units specially designed to analyze gases.
The Karl Fischer technique was invented in 1935 by Karl Fischer, a German scientist. The technique works by using either volumetric or coulometric titration. The solution used in the titration is comprised of four components, an alcohol (ROH), base (B), sulfur dioxide and iodine. These four components in the anode solution can react with water. Volumetric Karl Fischer calculate the water content based on the volume of regents need to convert water to BH+ROSO3−. The coulometric method measures the change in current between an anode and cathode to determine water content.
Karl Fischer is fast and accurate which has made it a popular choice for determining the water content in pharmaceutical products.