Karl Fischer Moisture Analysis

Why Karl Fischer specifically

Moisture content in a lyophilized peptide is a direct predictor of shelf life. Residual water drives hydrolysis of the peptide backbone, promotes aggregation, and can depress the glass transition temperature enough that a stored cake collapses. Karl Fischer titration exploits a stoichiometric reaction between iodine and water, so the number reported reflects water and only water. Loss-on-drying methods can over-report by counting residual solvents; thermogravimetric methods struggle at the low percentages typical of quality lyophilized product.

For pharmaceutical release testing, USP <921> identifies Karl Fischer as the reference method for water determination. Regulators increasingly cite it where water is a critical quality attribute.

What to expect on the report

• Sample identification and lot number
• Method used (coulometric or volumetric) with USP <921> reference
• Water content in mg/g and % w/w, with duplicate values and mean
• Instrument model and calibration status
• Analyst signature, report date, and method validation attestation
• Raw data available on request

When to include Karl Fischer in your panel

Karl Fischer is often bundled with HPLC purity, endotoxin (LAL), heavy metals, and residual solvents in a full injectable release panel. Full pricing lives at purity testing cost.