As a novice (a microbiologist), can anyone tell me what, if any, are the limitations of LCMS.
Thanks,

Joshua

the main limitation is that its not suitable for biologists;-)

Don't quite agree with the anonymous. LCMS is now a useful tool for the majority of life scieces.

Speaking about limitations you have here two different techniques (the LC and the MS) which each one has its own limitations. As LC limitations are more or less known and discussed all the time in this forum, I'll speak more for the MS limitations (lets say for electrospray quadrupole which are the most used).

Indeed, the hyphenation of LC (or other separation techniques) with MS was necessary to overcome limitations of the MS. These limitations are due to the instrinsic problems of MS to specifically analyse isomers and/or isobars, as well as problems related with the collisionally induced dissociation fragments, carbon-13 isotopes, cross talk, electrospray ion suppression etc.


So, in spite the specificity of (tandem) mass spectrometry it was quicly realised that it was extramely difficult (if not inpossible) to quantify the analytes or interest (in a matrix) by just infusing or by flow injection analysis (FIA) of our sample to the MS.

Other limitations now can be due to the ionisation sources used (which will allow at your compounds of interest to pass from the liquid phase to the gas phase as ions). For example ESI or APCI which are soft ionization methods might be difficult to ionize certain molecules (i.e. unpolar compounds etc). Different solutions have been though proposed to face these problems(derivatization, inorganic ion complexation etc).

But in spite the several advantages of LC-MS towards other LC detectors, the principal (not scientific) limitation which still avoids LC-MS to make part of every analytical (or others) laboratory in the word is its high price...

Kostas

Harsh statement, but I feel nobody, when dealing with unknowns, will do LCMS voluntary!!!. Why are there so many different ionization techniques?...I suspect the reason is that there is no "universal" ionization technique available such as EI in GC. LCMS for target compound analyses is fine, but I suspect much cheaper detectors often can do the job equally well.
I would still like to see the identification of complete unknowns from first principles (like in GCMS)...until then I'll keep my distance from LCMS

Multiple ionization methods exist because not all compounds can be ionized the same way. GCMS is not capable of ionizing all compounds; the range is rather limited. For larger compounds with higher boiling points, LCMS is much more useful than GCMS. Furthermore, the softer ionization of LCMS allows for better identification of the molecular weight. Fragmentation can be increased to further identify molecules. I rather enjoy identifying complete unknowns using LC/MS and LC/MS/MS.

Message to a Anonymous (January 14 9 PM)
I work in the development department of a fine chemichal company. We have a HPLC/MS (ION TRAP) since april and I would like to say that we have resolved structures always considered as unknown (even by HRMN or CRMN). Of course, others that are still unknown mainly because they can not be ionizated well (or we don't have enough experience with the equipment).

Depending on the kind of substances you are working with I enocurage to make a prove with any brand: they would be happy to test their product and habbilities with a unknown sample.

KAF

Just to clarify further for the MS hater who said "?...I suspect the reason is that there is no "universal" ionization technique available such as EI in GC". EI is available for LC, and just like for GC that technique has some limitations. Electrospray and APCI extend the the ionization capabilities of LC/MS way past that of the "universal" EI in GC. I will agree that in many cases traditional detection (RI, UV, FLD, PDA, ECD, ELSD "Why are there so many different ionization (detection) techniques?") techniques give more than enough information but not always. It is those times where MS is not only usefull but vital.