Counterfeit peptide (revision 9)

A counterfeit peptide is material misrepresented as to what it is or where it came from. Three forms are usually distinguished: substitution of a different compound, dilution of the correct compound with an undeclared bulking agent, and misrepresentation of origin where the compound is correct but the stated source is not.^[1]

The determination that detects substitution is identity — mass confirmation, and where available sequence confirmation — not purity. A substituted compound analysed alone will return an excellent area percent figure, because it is a pure sample of whatever it actually is.^[2]

Dilution is detected by content rather than by purity, for the same reason underfilling is: a bulking agent that does not absorb at the detection wavelength is invisible to a chromatographic purity determination. See Underfilling.

Substitution replaces the ordered compound with a different one, usually cheaper and often structurally unrelated. Because purity determinations are normalised and identity is frequently not determined, substitution can pass every check a purchaser typically makes.^[2]

Identity determination is the remedy and is not expensive relative to the purchase. A mass determination compares the observed molecular mass with the calculated one; agreement to within a few daltons excludes most substitutions outright. It does not exclude an isobaric substitution — a different molecule of the same mass — for which sequence-level confirmation is required.

The confounding case is a peptide of similar mass in the same family. Analogues within the incretin class differ by hundreds of daltons and are readily distinguished; a deletion sequence of the intended peptide differs by a single residue and is a synthesis defect rather than a counterfeit, though the analytical challenge is comparable. See Analytical method validation.