Dear Cletus,

Gas chromatography/mass spectrometry (GC/MS) is routinely used for identifying volatile and non-polar components, and the characterization of trace polar components is usually achieved by liquid chromatography/mass spectrometry (LC/MS).  

GC/MS is most useful for the analysis of trace amounts of organically extractable, non-polar, volatile compounds and highly volatile compounds. However, GC/MS has limitations in the analysis of highly polar compounds due to their thermolability and low volatility. Compared to GC/MS,  LC/MS is a powerful tool for determining highly polar compounds in several matrices.

Carotenoids, esters, terpenes, waxes, volatiles, flavonoids, and lipids are parameters that you can measure by GC/MS. Organic acids, amines, polyamines, and ion species are parameters that you can measure by LC/MS. GC/MS sample preparation can sometimes occur using LC/MS, as the alcohols, alkaloids, amino acids, fatty acids, phenols, and steroids.

Sincerely yours, Homayoon.

NMR, FTIR methods are authentic methods to check the structure of an isolated compound.

LC-MS or GC-MS characterization methods are chosen on the basis of nature of bio-active compounds.

Dear Ukwubile,

It’s totally up to you that which are the compounds you are expecting to isolate. GC/MS can identify only non- volatile oily compounds while LC/MS does opposite. If you need to isolate any known compounds than you should do as per the compounds nature. If you want to isolate any new compound than you should go with both of these. In addition extraction process should be the same as the compounds nature. Hope this will help you.

If you still need any help, you can connect me.

I think LC-MS is better because bioactive compounds are usually fragile and can easily decompose at by heat required byGC -MS

GC-MS is preferred for volatile compounds while LC-MS is most suitable for non-volatile compounds.

I discussed this question in relation to half a century of failed searching for a putative hormone, in a RG article ' Putative inhibitors of the sodium-potassium pump in mammals: a review', DOI: 10.13140/RG.2.2.10992.35845. Project:

Inhibitors of the sodium-potassium pump in mammals.

Researchers did not seem to understand that liquid phase ionisation techniques, which are all soft, most definitely did not replace electron and chemical ionisation.

At the risk of being later accused of self-plagiarism, I'll just copy a paragraph of the current draft of a follow-up article (I mention textbook derivatisation methods and the better separations and retention data elsewhere):

Beginning in the 1980, 'soft' liquid-phase ionisation methods such as fast atom bombardment (FAB) had become the first choice for examining newly-isolated metabolites because, though they are not universal, they detect compounds that are not sufficiently volatile for direct insertion MS. With modern equipment they are less technically demanding for biomedical researchers and analysts. However, these methods do not provide library-searchable spectra or much structural information. Without going into detail, spontaneous and collisionally-induced ion fragmentations of ions formed by 'soft' methods are not generally structure specific; unlike electron ionisation (and very often chemical ionisation) used in GC-MS, they do not provide a unique fingerprint. The situation is well understood and often discussed in the field of clinical steroid analysis. The GC-MS methods [Shackleton 1986] were found to be impracticable for routine use. During the last two decades, LC coupled to MS – which inevitably involve 'soft' ionisation – has been adopted, replacing the inadequate immunoassay methods. However, even with sophisticated tandem MS, the risk of mistaken or false positive identifications is recognised. Several authors have provided reminders that GC-MS should be used when researching new or uncertain territory (Krone et al., 2010; Kushnir et al., 2011; Shackleton, 2010)⁠. This is also the case when litigation might be involved. An earlier review 'Chromatography of cardiac glycosides' published in 1990 (Vetticaden & Chandrasekaran, 1990)⁠, which demonstrates almost total ignorance of GC-MS, may reflect a lack of cross-fertilisation between the fields of plant and animal steroids.

Krone, N., Hughes, B. A., Lavery, G. G., Stewart, P. M., Arlt, W., & Shackleton, C. H. L. (2010). Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery tool in clinical steroid investigations even in the era of fast liquid chromatography tandem mass spectrometry (LC/MS/MS). The Journal of Steroid Biochemistry and Molecular Biology, 121(3), 496–504. https://doi.org/10.1016/j.jsbmb.2010.04.010

Kushnir, M. M., Rockwood, A. L., Roberts, W. L., Yue, B., Bergquist, J., & Meikle, A. W. (2011). Liquid chromatography tandem mass spectrometry for analysis of steroids in clinical laboratories. Clinical Biochemistry, 44(1), 77–88. https://doi.org/10.1016/J.CLINBIOCHEM.2010.07.008

Shackleton, C. (2010). Clinical steroid mass spectrometry: A 45-year history culminating in HPLC–MS/MS becoming an essential tool for patient diagnosis. The Journal of Steroid Biochemistry and Molecular Biology, 121(3–5), 481–490. https://doi.org/10.1016/J.JSBMB.2010.02.017

Vetticaden, S. J., & Chandrasekaran, A. (1990). Chromatography of cardiac glycosides. Journal of Chromatography B: Biomedical Sciences and Applications, 531, 215–234. https://doi.org/10.1016/S0378-4347(00)82285-9

for volatiles or compounds that can be volatile after appropriate derivatisation of course GC/MS. For the rest LC-MS/MS, however, the comprehensive and integrative metabolomic approach will be a good milestone.