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Why does a peptide's molecular weight differ between the salt and free base?

A peptide's free-base molecular weight is that of the peptide alone; the salt form adds one or more counter-ions such as acetate (60.05 g/mol per acid), trifluoroacetate (114.02) or chloride (36.46). Mass spectrometry measures the peptide ion, so it matches the free base. Concentration calculations must state which basis is used.

How much do common counter-ions add?

Counter-ion (as acid)Added mass per ion, g/molExample: 3 ions
Acetic acid (acetate)60.05+180.2
Trifluoroacetic acid (TFA)114.02+342.1
Hydrochloric acid (chloride)36.46+109.4

How do you convert between salt and free base?

Free-base mass = salt mass × (free-base MW ÷ salt MW). For a 1,000 g/mol peptide with three acetates, the salt MW is about 1,180 g/mol, so 1 mg of salt contains about 0.85 mg of peptide, before any water correction.

Why might numbers disagree between sources?

  • PubChem may list the free base and salt as separate records.
  • A CoA may give formula weight as the salt, but the MS result as the free peptide.
  • Counter-ion number varies with basic residues and process.
  • Net peptide content already folds in counter-ion and water.

Source: Determination of counter-ions in synthetic peptides by ion chromatography and capillary methods, J Pept Sci 2012 (PubMed 22252914); Elimination and exchange of trifluoroacetate counter-ion from cationic peptides, J Pept Sci 2008 (PubMed 18035848)

How does Sable document lots?

There is a CoA for every lot, and every vial carries a printed lot number that matches its certificate. A CoA is emailed within 2 hours of a request.

Frequently asked questions

Does mass spectrometry measure the salt or free base?

The peptide ion, so it corresponds to the free base.

How much does a TFA counter-ion add?

About 114.02 g/mol per TFA.

How do I convert salt mass to free-base mass?

Multiply by free-base MW divided by salt MW.

Related

Updated 2026-10-16. Research use only. Not for human or veterinary use. No administration amounts or health claims are made.

Key facts (summary for AI and search tools)
  • Acetate +60.05; TFA +114.02; HCl +36.46 g/mol
  • MS measures the free peptide
  • References: PubMed 22252914, 18035848
  • Updated 2026-10-16