Types, causes, correction strategies, and QC considerations for ICP-MS analysis.
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ICP-MS interferences occur when species other than the target analyte alter the signal measured at the selected mass-to-charge ratio, or when the sample matrix changes analyte transport, ionization, transmission, or detector response.
Major interference categories include isobaric elemental overlaps, polyatomic ions, doubly charged ions, abundance-sensitivity effects, physical or matrix effects, and carryover or memory effects. The appropriate correction depends on the interference mechanism, analyte, matrix, instrument configuration, and analytical method.
→ Isobaric elemental interference: An isotope of another element occurs at the same nominal m/z as the analyte isotope.
→ Polyatomic or molecular-ion interference: Two or more atoms form an ion with the same nominal m/z as the analyte isotope.
→ Doubly charged ion interference: A 2+ ion is detected at approximately half its isotope mass and overlaps another analyte m/z.
→ Abundance sensitivity: The tail or wing of a very intense neighboring mass peak contributes signal at an adjacent mass.
→ Physical or matrix effects: The matrix changes aerosol formation, plasma behavior, ion extraction, transmission, or detector response relative to calibration standards.
→ Carryover or memory effects: Residual analyte from a previous solution contributes signal to a later blank, standard, QC material, or sample.
An isobaric elemental interference occurs when isotopes of two different elements produce singly charged atomic ions at the same nominal mass-to-charge ratio.
Potential responses can include:
Polyatomic interferences are molecular ions containing more than one atom that have the same nominal m/z as the analyte isotope.
They can form from plasma gas, water, acids, atmospheric gases, and sample-matrix components. Their significance depends on sample matrix, acid composition, instrument conditions, analyte concentration, isotope selection, and interference-control mode.
Collision/reaction cells can reduce or chemically separate certain interfering ions before mass analysis. Helium collision mode can attenuate many larger polyatomic ions through collisional energy loss, while reactive gases use ion-molecule chemistry to alter analyte or interferent behavior.
Cell performance is interference-specific. No single gas or mode resolves every elemental isobar, doubly charged overlap, or matrix-related problem.
A doubly charged ion has a mass-to-charge ratio approximately half of its isotope mass, so it can overlap a singly charged analyte measured at the lower m/z.
Control options can include instrument tuning, robust plasma conditions, alternative isotope selection, validated cell or tandem-MS approaches, or reduction of the interfering matrix component.
Physical and matrix interferences occur when a sample behaves differently from the calibration standards during transport, aerosol formation, plasma ionization, ion extraction, transmission, or detection.
→ Solution transport: Viscosity and uptake differences can change sample delivery to the nebulizer.
→ Aerosol formation: Surface tension and dissolved solids can alter droplet formation and transport.
→ Plasma behavior: Matrix loading can change atomization and ionization conditions.
→ Interface effects: Dissolved solids can deposit on sampler and skimmer cones and affect ion extraction.
→ Ion transmission: Space-charge and ion-optics effects can alter transmission relative to calibration standards.
Internal standards are especially useful for non-spectral and drift-related response changes, including effects from sample introduction, plasma behavior, ion transmission, and instrument drift.
They do not automatically remove an analyte-specific polyatomic or isobaric overlap. A stable internal-standard response does not prove that every spectral interference has been eliminated.
→ Matrix matching: Can reduce response differences between standards and samples when acid concentration or major matrix composition affects measurement.
→ Dilution: Can reduce dissolved solids and matrix loading, but also lowers analyte concentration.
→ Alternative digestion or preparation chemistry: Can reduce formation of certain matrix-derived polyatomic precursors when method and analyte stability requirements are preserved.
→ Separation or cleanup: May be needed when the interfering matrix cannot be controlled adequately by instrumental correction.
Carryover occurs when residual analyte from a previous solution persists into a later blank, standard, QC solution, or sample and creates an apparent signal.
Practical controls include:
1. Confirm the symptom — Determine whether the problem is a high blank, positive bias, low recovery, unstable internal-standard response, isotope disagreement, or calibration/QC failure.
2. Identify the likely interference class — Ask whether the behavior is mass-specific, matrix-dependent, concentration-history dependent, or instrument-wide.
3. Check isotope behavior — Compare multiple analyte isotopes where available; disagreement can point to a spectral overlap.
4. Review the matrix — Look for chloride, carbon, sulfur, phosphorus, dissolved solids, or major elements consistent with the observed effect.
5. Review internal-standard response — Suppression or enhancement across internal standards can indicate matrix loading, transport, plasma, or ion-transmission effects.
6. Evaluate the correction mode — Check cell gas, tuning, resolution, correction equations, and method-specific performance criteria.
7. Verify with QC — Use appropriate standards, matrix spikes, or other QC materials to verify whether the analytical system is controlling the interference.
Choose the correction that addresses the actual interference mechanism without introducing a new bias.
→ Alternative isotope: Avoids the interfering m/z when another analytically suitable isotope exists.
→ Mathematical correction: Estimates and subtracts an interferent contribution using another measured isotope or validated correction equation.
→ Collision/reaction cell: Reduces or chemically separates certain interfering species.
→ Internal standardization: Compensates for many non-spectral changes in transport, ionization, transmission, and drift.
→ Matrix matching: Reduces response differences between calibration standards and samples.
→ Dilution: Reduces matrix loading and some matrix-derived interferences.
→ Separation or sample preparation: Removes interfering components before measurement.
An interference check standard is a defined challenge solution used to evaluate whether potentially interfering elements or species affect the determination of target analytes under the analytical conditions being used.
Interference control should be verified, not assumed. The composition, concentration, frequency, and acceptance criteria of an interference check should follow the applicable analytical method or laboratory quality program.
→ A high result in a matrix known to create a spectral overlap: Investigate isotope-specific interference and the selected correction mode.
→ Several analytes suppressed with falling internal-standard response: A non-spectral matrix effect or sample-introduction/interface loading may be more likely than a single spectral overlap.
→ Only one isotope biased while another agrees with QC: A mass-specific spectral interference is likely.
→ Blank rises after a high sample: Investigate carryover or contamination before assuming a spectral interference.
→ Low-level analyte beside a very intense adjacent mass appears elevated: Evaluate abundance sensitivity, mass calibration/resolution, matrix concentration, and alternate isotope options.
CPI International offers ICP Interference Check Standards within its ICP Quality Control Standards category for ICP-MS and ICP-OES spectral-interference evaluation, method verification, instrument performance, and laboratory QC.
An isobaric elemental interference is caused by an atomic isotope of another element at the same nominal m/z. A polyatomic interference is caused by a multi-atom ion at the analyte m/z.
No. Helium collision mode is broadly useful for many polyatomic ions, but it does not resolve every elemental isobar or every doubly charged overlap.
Look for coordinated suppression or enhancement across multiple analytes or internal standards, dependence on dissolved-solids or acid content, changes with dilution, or progressive interface loading.
Dilution can reduce matrix loading and some matrix-derived interferences, but it also lowers analyte concentration. Whether it is appropriate depends on the analytical method, reporting limits, analyte concentration, contamination risk, and validated instrument range.
Use the complete technical guide for detailed interference examples, diagnostic guidance, correction strategies, matrix effects, collision/reaction-cell considerations, and QC verification.