LimsPulse
Chromatography

Liquid Chromatography–Mass Spectrometry (LC-MS / LC-MS/MS)

Couples an HPLC or UHPLC to a mass spectrometer, so each separated component is identified by its mass and measured with very high sensitivity. Used for impurity identification, nitrosamines and other trace impurities, and bioanalysis.

  • Pharmaceutical
  • Biopharmaceutical
  • Clinical and bioanalytical labs
  • Food safety
  • Environmental
  • Forensic and toxicology
Photo of a Liquid Chromatography–Mass Spectrometry (LC-MS / LC-MS/MS)
Photo: Sarka Na kopci, CC BY-SA 4.0 (cropped), via Wikimedia Commons
TROUBLESHOOTING

Common problems, causes and fixes

Loss of sensitivity
Likely causes
  • • Dirty ion source or cone
  • • Ion suppression from matrix
  • • Detector ageing
  • • Wrong tune or mass calibration
What to do
  • • Clean the source
  • • Improve sample clean-up or chromatographic separation
  • • Increase detector voltage within limits or replace the detector
  • • Re-tune and recalibrate
Unstable spray or noisy signal
Likely causes
  • • Partly blocked ESI needle or capillary
  • • Air in the LC flow
  • • Gas supply problems
What to do
  • • Clean or replace the needle
  • • Degas solvents and purge the LC
  • • Check nitrogen pressure and purity
Mass shift / wrong m/z
Likely causes
  • • Calibration out of date
  • • Room temperature change affecting the analyser
What to do
  • • Recalibrate with the reference solution
  • • Stabilise room temperature; use a lock mass on HRMS
High background ions
Likely causes
  • • Contaminated solvents or additives
  • • Plasticisers from tubing or containers
  • • Column bleed
What to do
  • • Use fresh LC-MS grade solvents
  • • Use MS-compatible tubing and glass containers
  • • Condition or replace the column
Vacuum fault
Likely causes
  • • Leak at a seal
  • • Rough pump failing
  • • Turbo pump fault
What to do
  • • Stop work and contact service
  • • Check pump oil and running noise
  • • Do not run samples until vacuum is restored
In LimsPulse · Calibration Management

Keep every LC-MS in control: usage logs, calibration and maintenance schedules, and automatic blocking of overdue instruments.

See how