Heavy metals testing and ICP-MS on a certificate of analysis

Some COAs include a line for heavy metals or elemental impurities. It is usually measured by ICP-MS, and it answers a narrow question: how much of a specific list of elements is in the sample?

Where metals come from

Synthetic peptides do not contain metals by design. Trace amounts can come in from reagents, catalysts, water, steel equipment, or glass. A metals test checks that those sources did not leave measurable residue.

What ICP-MS is

ICP-MS stands for inductively coupled plasma mass spectrometry.

1. Digestion. The sample is broken down, usually in concentrated nitric acid with heat or microwave energy, so that everything is in solution and the organic material is destroyed.
2. Plasma. The solution is sprayed into an argon plasma at several thousand degrees. Every element is atomized and ionized.
3. Mass spectrometer. The ions are sorted by mass-to-charge ratio and counted.
4. Calibration. Counts are converted to concentrations against standards of known concentration for each element.

Because it detects ions by mass, ICP-MS can measure many elements in one run, at very low levels: parts per billion or lower for many of them.

ICP-MS vs ICP-OES

	ICP-MS	ICP-OES
Detects	Ions, by mass	Light emitted by excited atoms, by wavelength
Typical sensitivity	Parts per billion to parts per trillion	Parts per million to high parts per billion
Best for	Trace and ultra-trace levels	Higher concentrations and samples with a heavy matrix
Known issues	Interferences from ions of similar mass, handled with collision cells	Spectral overlaps between emission lines

For small samples of a high-purity material where metals are expected to be very low, ICP-MS is the usual choice.

Which elements

Reports often lead with four: lead (Pb), arsenic (As), cadmium (Cd) and mercury (Hg). These are the elements most commonly singled out in elemental impurity guidance. A report may add others, such as nickel, chromium, copper or palladium, depending on what might be present from the process.

A report covers only the elements listed. An element not on the list was not measured.

Reading the line

Element	Specification	Measured value	Notes
Lead	stated limit, µg/g	e.g. less than 0.05 µg/g	"Less than" means below the reporting limit
Arsenic	stated limit	e.g. 0.08 µg/g	A measured figure

Units to know:

• µg/g is the same as parts per million (ppm) by weight
• ng/g is parts per billion (ppb)

Labs often report "less than LOQ" (limit of quantitation) when a metal is too low to measure precisely. That is a sensitivity statement for that run, not a zero.

What the line does not cover

Metals testing does not speak to purity, identity, endotoxin or microbial status. It is one panel among several, and it is often absent from routine research COAs. Its absence means there is no metals data for that lot, nothing more.