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
LEARN & PRACTICE

Test your LC-MS knowledge

Multiple-choice questions

Pick an answer to see whether you are right and why.

  1. Q1. What does a mass spectrometer actually measure?

    basic

  2. Q2. Which buffer should NOT be used in an LC-MS mobile phase?

    basic

  3. Q3. Electrospray ionisation in positive mode mostly produces which ion from a basic drug M?

    intermediate

  4. Q4. Which mode of a triple quadrupole is preferred for trace quantitation of nitrosamines?

    intermediate

  5. Q5. Theoretical m/z 609.2807, measured 609.2815. The mass error is about:

    advanced

  6. Q6. What is the best way to correct for ion suppression in quantitative LC-MS?

    intermediate

Viva questions

Think of your answer first, then open it to compare.

  1. 1. How would you use LC-MS to identify an unknown degradation product found in a stability sample?

    Run the sample on an MS-compatible version of the method, obtain the accurate mass of the unknown on a high-resolution instrument, propose an elemental formula, acquire MS/MS fragments, compare with the parent drug's fragmentation and known degradation chemistry, and confirm with a synthesised or purchased reference standard.

  2. 2. Why is a divert valve used at the start of an LC-MS run?

    Salts and polar matrix components elute at the solvent front. Diverting them to waste keeps the ion source clean and maintains sensitivity.

  3. 3. Compare a triple quadrupole with a Q-TOF for pharmaceutical work.

    A triple quadrupole has unit resolution but excellent sensitivity in MRM, ideal for targeted trace quantitation (nitrosamines, bioanalysis). A Q-TOF gives high resolution and accurate mass for formula assignment and unknown identification, with full-spectrum data, but is usually less sensitive for targeted quantitation.

In LimsPulse · Calibration Management

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

See how