Water content

A lyophilisate is hygroscopic by construction: freeze-drying leaves a porous cake with enormous surface area, which is exactly what makes it reconstitute quickly and also what makes it take up atmospheric moisture within minutes of exposure.

That water is mass. It sits in the denominator of every content calculation, it is invisible to chromatographic purity, and it is the reason raw powder must ship in sealed glass rather than in a plastic bag. Powder that absorbed water in transit reports low on content, and the certificate would be describing the shipping rather than the product.

Reporting on an anhydrous basis is possible and sometimes preferable, but only once water has actually been measured. A result quoted as anhydrous without a water determination behind it is an assumption dressed as a correction.

Coulometric titration generates iodine electrochemically in situ and calculates water from the charge passed, using Faraday's law. It suits samples with low water content and small available mass, which describes most peptide work.

Volumetric titration adds iodine-containing reagent from a burette and suits samples with higher water content and generous sample availability. Both are specific to water through the same underlying reaction, which is what distinguishes Karl Fischer from loss on drying.

Loss on drying measures everything volatile at the drying temperature, so residual solvent is counted as water. Where both determinations are run, the difference between them is itself informative.