Underfilling (revision 13)

Underfilling is the delivery of less material in a container than the quantity stated on its label. It is a distinct failure from impurity and is invisible to the determination most often supplied: area percent purity is normalised and does not change with the amount of material present.^[1]

The quantity a purchaser cares about is the mass of peptide in the vial. That is the product of three things — the fill mass, the peptide content of the solid, and the purity — and a certificate reporting only the last of these constrains it hardly at all.^[1]

Underfilling has been documented in independently examined research-chemical material. It is also the failure most easily checked without a laboratory, since it requires only a balance of adequate resolution and an empty vial of the same type for tare.^[2]

Chromatographic purity is computed as the area of the main peak divided by the total integrated area, expressed as a percentage. Both terms scale with the amount injected, so the ratio is invariant to concentration over the linear range of the detector.^[3]

A consequence is that a half-filled vial and a correctly filled vial of the same material give the same purity figure. The determination is answering a question about composition, and fill is a question about quantity.

The same reasoning applies to identity determinations. A mass spectrum confirms what a molecule is, not how much of it there is, unless the method is explicitly quantitative against a standard.

The arithmetic that matters is straightforward. A vial containing 5.0 mg of solid at 80% peptide content contains 4.0 mg of peptide, whatever its purity figure says; the same vial at 60% content contains 3.0 mg. Content in the 70–90% range is ordinary for a trifluoroacetate-salted lyophilisate, and figures below that are not rare.^[1]

• Peptide content
• Area percent purity
• Vial filling and stoppering
• Certificate of analysis
• Trifluoroacetate counterion