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Method / concept

ESI-MS (mass spectrometry)

Electrospray-ionization mass spectrometry (ESI-MS) confirms a compound’s identity by measuring the mass of its molecules. The sample is sprayed from a fine charged capillary so it enters the instrument as gas-phase ions, and the mass spectrometer then sorts those ions by their mass-to-charge ratio (m/z). For a peptide of known sequence the expected masses can be calculated in advance, so identity is confirmed when the observed spectrum matches the expected series.

Definition. Electrospray-ionization mass spectrometry; confirms a compound's identity by measuring its molecular mass.

How it works

Electrospray ionization is a “soft” ionization method. A solution of the peptide is pushed through a needle held at high voltage, producing a fine mist of highly charged droplets; as the solvent evaporates the droplets shed charge and shrink until bare, intact, multiply-charged ions remain. “Soft” means the molecule is ionized without being fragmented, so its intact mass is preserved.

Peptides characteristically pick up more than one proton, giving a series of ions such as [M+H]⁺, [M+2H]²⁺, and [M+3H]³⁺. Each appears at a different m/z because the charge (z) in the denominator differs, so a single compound produces a ladder of related peaks rather than one, and the underlying neutral mass can be reconstructed from any two members of the series.

The analyser separates ions by m/z and the detector records their abundance, producing a mass spectrum — abundance plotted against m/z. Because the expected m/z values follow directly from the molecular formula, an observed peak matching the expected [M+H]⁺, within the instrument’s mass accuracy, confirms that the molecule present has the expected mass.

Two mass conventions matter when comparing values: the monoisotopic mass, calculated from the most abundant isotope of each element, and the average mass, weighted over natural isotope abundances. High-resolution instruments resolve the isotope pattern and are compared against the monoisotopic value; the two figures differ slightly and should not be mixed.

Why it matters

Mass spectrometry answers the identity question a purity method cannot: it indicates whether the molecule you have is the molecule you intended, independent of how much of it is present. A preparation can be highly pure by HPLC and still be the wrong compound, and ESI-MS is the check against that.

Because the expected masses are computed from the sequence, ESI-MS is effectively a pre-registered test — the target value is fixed before the measurement is made, so a match is meaningful rather than post-hoc. A deletion, an extra residue, or an unexpected modification shifts the observed mass in a predictable, diagnosable direction.

Identity and purity together — mass by ESI-MS and area percent by RP-HPLC — are the two independent measurements a characterization record is built on. Neither substitutes for the other.

At Lineará

Every compound page publishes the expected ESI-MS series for the molecule, and the certificates confirm identity by comparing the observed mass-to-charge ratio against that expected series.

The compound identifiers — molecular formula, monoisotopic mass, and expected m/z — are derived by construction and reconciled against an independently computed formula and mass, so the expected value a certificate is checked against is itself a checked value.

Frequently asked questions

What does ESI-MS confirm?
Identity. It measures the mass of the intact molecule and compares the observed mass-to-charge ratio against the series expected from the compound’s molecular formula. It does not measure purity — that is done separately by RP-HPLC.
Why do peptides show several peaks in one spectrum?
Peptides commonly acquire more than one proton, producing a series of multiply-charged ions such as [M+H]⁺, [M+2H]²⁺, and [M+3H]³⁺. Each falls at a different m/z because the charge differs, so one compound yields a ladder of related peaks from which the neutral mass is reconstructed.
What does soft ionization mean?
It means the molecule is converted to a gas-phase ion without being broken apart, so its intact mass is preserved for measurement. Electrospray is a soft technique, which is why it is well suited to intact peptides.
What is the difference between monoisotopic and average mass?
Monoisotopic mass is calculated using the single most abundant isotope of each element; average mass is weighted across each element’s natural isotope abundances. High-resolution measurements are compared against the monoisotopic value, and the two figures should not be interchanged.

Research professionals only

Every term, on the record

Definitions are analytical and characterization-only, and trace back to the compounds and methods they describe.

áFor Research Use Only · Not for human or veterinary use · Not for diagnostic or therapeutic use