Water content by Karl Fischer titration

Quantifying residual water in lyophilised material, which changes every mass-based calculation.

Purpose

Quantifying residual water in lyophilised material, which changes every mass-based calculation.

This page exists so that a discussion about a number can start from a shared understanding of what produced it. It is written for a reader who is technically literate but not a practising analyst.

How it works

Lyophilised peptide is not dry. Residual water of a few per cent is normal and considerably higher figures are not unusual. Karl Fischer titration quantifies it specifically, as opposed to loss on drying, which measures everything volatile.

This matters because a label claim in milligrams refers to peptide, while the contents of the vial are peptide plus water plus counter-ion plus any excipient. Two vials at identical chromatographic purity can contain measurably different amounts of peptide if their water contents differ.

What determines the result

It is one of the few certificate fields that lets you reconcile a content assay with a label claim, and one of the least frequently reported.

Typical criteria

These are typical values, not universal standards. The criteria that apply to a specific result are the ones in the validated method that produced it, which is why a report without a method identifier is harder to interpret than one with.

What it cannot tell you

Every analytical method answers one question. The most common error in this community's discussions is treating an answer to one question as an answer to another: a mass match read as a purity result, a purity figure read as a content determination, a sterility test read as a guarantee of safety.

When you read a report, write down which question was asked. The rest follows.

Related pages

Other method notes in this commons cover the neighbouring techniques, and the certificate interpretation page covers how these results get reported. The impurities subcategory is where the discussion happens.