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TSMS-ANL-003

Liquid Chromatography–Mass Spectrometry (LC-MS) Study Guide

School of Analytical Chemistry · Analytical Chemistry Foundations · Intermediate–Advanced

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Learning objectives

  • Explain how LC and MS are coupled.
  • Describe electrospray ionization.
  • Interpret mass-to-charge ratio conceptually.
  • Explain peptide charge states and deconvolution.
  • Distinguish TIC, EIC, and mass spectra.
  • Describe how MS/MS supports sequence-related evidence.

Executive summary

LC-MS combines liquid chromatography with mass spectrometry.

The chromatograph separates components in time. As each compound elutes, the mass spectrometer converts it into ions and measures mass-to-charge ratio.

This combination supports:

- intact-mass confirmation,
- identity assessment,
- impurity characterization,
- degradation-product investigation,
- sequence-related fragmentation analysis,
- quantitative methods.

Key takeaways

  • LC-MS combines separation with mass analysis.
  • Electrospray ionization is well suited to peptides.
  • Peptides commonly produce multiple charge states.
  • Deconvolution reconstructs neutral mass.
  • MS/MS supports structural characterization.
  • Interpretation requires calibration, controls, and scientific context.

Self-review questions

  1. What does m/z represent?
  2. Why do peptides produce several charge states?
  3. What is the purpose of deconvolution?
  4. How does an EIC differ from a TIC?
  5. What additional information does MS/MS provide?

Use the full lesson to verify your answers.