LC/LC‑MS Carryover Hunter

Pain point

Peaks appear in blanks following high samples, producing false positives and biasing quantification.

Repro/diagnostic steps

1. Run: high sample → blank series; quantify carryover decay.
2. Isolate: injector/autosampler vs column vs solvent contamination using bypass/swaps.
3. Inspect hardware: needle guide/seat, seals, and tubing connections for "reservoir" volumes.

Root causes (common)

• Inadequate wash solvent strength or wash duration.
• Worn injector/rotor seals and contaminated needle/seat components.
• Poorly seated fittings creating dead volumes that retain sample.

Fix workflow

1. Choose wash solvents based on analyte chemistry; verify needle wash is actually applied.
2. Replace/clean wear parts on a maintenance cadence (rather than only reacting).
3. Reduce dead volumes by reseating fittings and simplifying plumbing.
4. Validate with a standardized carryover test sequence.

Expected result

• Carryover in post-blank falls below method acceptance thresholds and remains stable over time.

References

• https://help.waters.com/help/en/product-support/alliance-is-system-support/715008450/CBAFCF3.html
• https://www.chromforum.org/viewtopic.php?t=79744&view=next
• https://knowledge1.thermofisher.com/Mass_Spectrometry/Mass_Spectrometry_Knowledge/Carryover_and_Contamination