Definition
Karl Fischer titration measures water content using a reaction in which iodine oxidises sulfur dioxide in the presence of water, a base and an alcohol. Each molecule of water consumes a fixed amount of iodine, so the endpoint gives a precise water figure. Volumetric titration suits samples with higher water content, while coulometric titration, which generates iodine electrochemically, detects microgram quantities and suits small peptide samples. Lyophilised peptides typically contain a few percent residual water, and because they are hygroscopic, the figure can rise after opening. Water content contributes to the gap between gross powder mass and net peptide content, and some certificates of analysis report it alongside purity and counter-ion results.