Loss on drying (revision 13)
Old revision·23:03, 1 Feb 2025·HOMA_Hettie
| Loss on dryingCompendial test | |
|---|---|
| Abbreviation | LOD |
| Measures | Total volatile mass lost under defined conditions |
| Contrast with | Karl Fischer titration, which measures water specifically |
| Compendial chapter | USP <731> |
| Analytical method infobox · conventions | |
Loss on drying determines the mass a sample loses when heated under defined conditions of temperature, pressure and time. It is simple, requires no specialised reagent, and is widely reported on peptide certificates.[1]
It is not a water determination. The mass lost comprises water and any other volatile component — residual acetonitrile, acetic acid, ammonia from a salt-exchange step — so a loss-on-drying figure is an upper bound on water content rather than a measurement of it. Karl Fischer titration measures water specifically and will generally give a lower number on the same material.[2]
For peptides the two are frequently confused, and a certificate reporting "water: 6.2% (LOD)" is reporting something other than water. The distinction matters because water is subtracted in calculating peptide content, and using a loss-on-drying figure for that subtraction understates the peptide.[3]
Method
[edit]A weighed sample is dried to constant mass under stated conditions — an oven at a specified temperature, or a desiccator over a specified desiccant, or under vacuum — and the mass difference expressed as a percentage of the starting mass.[1]
The conditions are part of the result. Drying at 105 °C removes more than drying at 60 °C; drying under vacuum removes more than at atmospheric pressure. A figure quoted without its conditions is not comparable with another figure quoted without its conditions.
For peptides the conditions must be gentle enough to avoid decomposition. Aggressive drying can cause loss of mass through degradation rather than through evaporation, which inflates the figure and damages the sample; vacuum drying at moderate temperature is the usual compromise.[3]
Why the distinction from water matters
[edit]Peptide content is calculated by subtracting the non-peptide fractions — water, counterion, residual solvent, inorganic salt — from unity. Each must be determined by a method specific to it, or the subtraction double-counts or under-counts.[3]
| Determination | What it captures |
|---|---|
| Loss on drying | Water plus all volatiles, together |
| Karl Fischer titration | Water only |
| Residual solvent, by gas chromatography | Named organic solvents, individually |
| Counterion assay | Trifluoroacetate counterion or acetate content |