Similarities and Dissimilarities between GC/MS and LC/MS

Similarities and Dissimilarities between GC/MS and LC/MS

GC and HPLC are both chromatography separation techniques which are immensely popular with the analytical chemist. Over the past several decades Mass spectroscopy has contributed significantly to the scope of applications of both GC and HPLC. Hyphenated mass spectroscopy techniques have made possible separation and identification of complex mixtures in a matter of minutes which in earlier days would take several hours if not days.

Gas chromatography – Mass spectroscopy (GC/ MS) has proved to be a valuable tool for analysis of volatile compounds which are stable enough to withstand the high temperatures during gas chromatographic separations. On the other hand Liquid chromatography – mass spectroscopy (LC/MS) is suitable for compounds of lower volatility whose volatility cannot be increased even on derivatization.

Both GC/ MS and LC/ MS are advanced chromatographic techniques which are used for separation of complex sample mixtures. After ionization the ionized fragments are led through mass filters to the detector.

The number of dissimilarities is more and need a clear understanding to help you take a judicious choice in selection of the technique to meet your analysis requirements.


LC/ MS systems are more expensive in comparison to GC/MS. They require specialized operator training as well as more maintenance. On the other hand GC/MS is simpler to operate and requires less maintenance as only components like septa and liners need replacement from time to time to maintain optimum performance.

Mobile Phase

It is obvious that GC/ MS makes use of an inert gas as a carrier whereas LC/ MS uses a mixture of liquids with or without buffers or additives as a carrier phase

Nature of Compounds

GC/ MS is suitable for analysis of samples of essential oils, fatty acids, alcohols, polysaccharides, esters, terpenes , flavours and gases. LC/ MS has no known applications for analysis of gases but common applications include nonpolar compounds such as a amines, nucleotides, nucleosides, steroids and other molecules of biological interest.

Vacuum Requirements

Vacuum requirements are more stringent for LC/ MS as any liquid in the carrier stream needs to be removed totally before sample constituents are allowed to proceed to the ionization chamber. This requires fine control of vacuum through multiple pumps in LC/ MS. In case of GC/MS as the carrier is a gas such high vacuum requirements are not necessary.

Ionization Techniques

Ionization techniques in mass spectroscopy were discussed in the earlier article’ Popular ionization techniques in mass spectroscopy’. Electron impact is the common ionization mode in GC/ MS and chemical ionisation is also available as a soft ionization option. Electrospray ionization and atmospheric pressure chemical ionization are preferred ionization techniques in LC – MS systems

Spectral Libraries

Spectral match is facilitated through the availability of libraries on classes of compounds for positive identification of components. Such databases are commonly available from global standard bodies such as NIST. However, such libraries are hardly available for LC/ MS systems but you can create your own spectral search libraries depending on your analytical requirements

Typical analysis such as forensic applications require confirmation on the presence or absence of specific substances instead of complete sample composition so GC/ MS is preferred because of its lower cost, ease of operation and maintenance. However, for demanding applications requiring identification and quantification at low concentrations of known and unknown components LC/ MS is the preferred choice.

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  1. can you please let me work as an intern in your laboratories?
    i am pursuing Masters in analytical Chemistry from N.I.T Warangal

    1. Hi Mayank,
      Sorry we shall not be able to entertain your request as we have no such provision. However you may send your CV for necessary consideration to [email protected] if you wish to be considered for placement


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