Why does a high purity figure not rule out metal contamination?

Because the purity figure is calculated from chromatographic detector response, and elemental residues largely do not produce a chromatographic response. They are invisible to the calculation rather than absent from the sample. Only a separate elemental method can answer the question.

What does "below the limit of detection" actually tell me?

That the quantity present, if any, is under the smallest amount that instrument and method could have found. It is a bound rather than a zero, which is why the limit itself should be printed. A very low limit is a strong statement; an unstated limit is not a statement at all.

Is a broad screen better than testing the four regulated elements?

It is more informative, because it can surface residues nobody was looking for — a catalyst metal specific to one synthesis route, for instance, would not appear on a four-element panel. The targeted panel answers its own question perfectly well; it just answers a narrower one.

Analysis & documentation

Heavy metal screening: what chromatography cannot see

Updated August 13, 2026

A purity figure cannot show elemental residues, because they do not behave like chromatographic peaks. A separate instrument answers a separate question.

The blind spot

Chromatography separates a sample and reports what the detector responds to. Elemental residues largely do not respond, do not resolve as peaks, and therefore do not appear in a purity calculation at all.

This is not a shortcoming of the method. It is a category difference: the instrument is answering a question about molecules, and metals in a sample are not a molecular impurity of the kind it is built to find. A sample can report a very high purity figure and carry elemental residue that the figure had no way to represent.

What ICP-MS does

Inductively coupled plasma mass spectrometry takes the sample apart entirely. A plasma running at several thousand degrees breaks it into individual atoms and ionizes them, and a mass spectrometer then counts those ions by mass.

Because the molecule is destroyed before measurement, nothing about its structure matters. Whatever elements are present are counted, in parts per billion and lower. That destructive step is why it can find what chromatography cannot: it stops asking what the sample is and asks only what it is made of.

Where the residues come from

Elemental contamination in synthetic peptide material has ordinary industrial sources rather than dramatic ones.

Catalysts and reagents used during synthesis, some of which are metal-based by design
Equipment surfaces — stainless steel, valves, tubing — contributing trace amounts through ordinary contact and wear
Water and solvents, which carry whatever their own purification left behind
Container and closure materials, particularly where material sits for long periods

Broad screen versus targeted panel

There are two ways to run the analysis, and the difference matters when reading a certificate.

A targeted panel measures a defined list — commonly the four that regulatory frameworks single out for the greatest attention: lead, arsenic, cadmium and mercury. It answers a specific question well and says nothing about anything outside the list.

A broad elemental screen measures across most of the periodic table at once. It is more informative precisely because it is not looking for anything in particular: a residue nobody thought to suspect still shows up. The pharmaceutical framework for elemental impurities, ICH Q3D, works through risk assessment across a wide set of elements for the same reason.

Reading the report

An elemental report is mostly a long column of numbers near zero, which makes the few things worth attending to easy to miss.

The detection limit for each element. A result below the limit is bounded by that limit — the limit is the real information.
Which elements were included. A screen naming its coverage is checkable; "heavy metals: pass" is not.
Units, consistently applied. Parts per million and parts per billion differ by a factor of a thousand, and a report mixing them without saying so is hard to read correctly.
Whether the figure is for the element or a compound of it, which changes what the number refers to.

Common questions

Why does a high purity figure not rule out metal contamination?: Because the purity figure is calculated from chromatographic detector response, and elemental residues largely do not produce a chromatographic response. They are invisible to the calculation rather than absent from the sample. Only a separate elemental method can answer the question.
What does "below the limit of detection" actually tell me?: That the quantity present, if any, is under the smallest amount that instrument and method could have found. It is a bound rather than a zero, which is why the limit itself should be printed. A very low limit is a strong statement; an unstated limit is not a statement at all.
Is a broad screen better than testing the four regulated elements?: It is more informative, because it can surface residues nobody was looking for — a catalyst metal specific to one synthesis route, for instance, would not appear on a four-element panel. The targeted panel answers its own question perfectly well; it just answers a narrower one.

Check a certificate

Certificates are published per lot. The number printed on a vial retrieves the analysis of that specific batch.

Look up a lot number

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