Mass spectrometry for peptides, explained simply

If you've ever stared at a CoA and wondered what '4731.4 Da observed vs 4731.2 Da theoretical' means, this guide is for you.

What a mass spectrometer does

A mass spectrometer ionises molecules and measures their mass-to-charge ratio. For peptide identity, the relevant output is the observed mass of the molecule, which should match the theoretical mass calculated from the peptide's amino-acid sequence.

Monoisotopic vs average mass

Two mass values appear on CoAs:

For a peptide around 4000-5000 Da, the two values differ by 2-3 Da, so make sure the CoA states which it's reporting.

Acceptable tolerance

A modern LC-MS instrument should match the theoretical mass to within 0.5 Da or better. If a CoA reports the observed mass 5+ Da away from theoretical, the molecule is not what the label says.

Common peptide masses

What if the CoA only has a purity number?

Then you have no identity proof, only a purity number for "something". Purity without identity is the single most common gap in vendor CoAs.

Frequently asked questions

Is LC-MS the same as MALDI-TOF?

Both are mass spectrometry, but different ionisation methods. Either confirms identity if run properly.

Can mass spec detect a fake peptide?

Yes: if the vial contains a different molecule than the label, observed mass will not match theoretical mass.

Why do some CoAs skip identity testing?

Cost. A purity-only HPLC run is cheaper than HPLC plus LC-MS, so cut-rate labs skip it.