What is LC/MS/MS

[LC_Trouble]

Hi Everyone,

I would like to know the diffrence between Lc/MS and LC/MS/MS.

Thanks.

[tom jupille]

About $150,000.

Assuming you wanted a serious answer, in LC-MS, there is only a "single stage" of mass spectrometry after the HPLC system. In LC-MS/MS, there is a "tandem" mass spectrometer. The most common implementation is a triple quadrupole system. Molecules coming out of the LC are ionized then separated in the first quadrupole. Ions coming out of the first quadrupole go into the second quadrupole where they are fragmented. The fragments are fed into the third stage where they are separated.

As you might imagine, the "triple quad" LC-MS/MS systems are considerably more complex and expensive than a "single quad" LC-MS. They are capable of much greater sensitivity for complex samples.

[MIB_EO]

I wouldn't say that MSMS is capable of better sensitivity, after all there are more instrument stages to go through each losing transmission efficiancy.

However What MSMS does that MS doesn't do is provide some structural information. Leading to a better determination of what your original ion was.

There can be many ions with an M/Z of 500+/-0.05 da, but only a few possabilities of those will have a fragment of 125.2 da, and only one with two or three specific fragments.

Depending on the specific instrument and software this can be used for analysing unique protein structure, or many other tasks.

[tom jupille]

I wouldn't say that MSMS is capable of better sensitivity, after all there are more instrument stages to go through each losing transmission efficiancy.

Actually what I said was "They are capable of much greater sensitivity for complex samples." (italics added). When you separate/fragment/separate, the noise (from similar mw garbage) attenuates faster than the signal (from the fragment you are monitoring).

[Kostas Petritis]

I think that Tom and MIB_EO are talking for two different types of MS/MS fragmentation.

Tom is refering to the MRM mode where (in a triple quadrupole instrument) you select one molecular ion in Q1 , fragment it in Q2 and select again one in Q3. Complex or not matrix, if you are able to obtain at least one relative high abunant fragment ion, you are almost garantee that you will have better LOD in the MS/MS mode than in MS only and this is particularly true for small MW ions where the background noise in the MS is particularly high. LOD improvent in this case can go up to 100 folds...

The reason of the sensity increase is what Tom mentioned which I quote "When you separate/fragment/separate, the noise (from similar mw garbage) attenuates faster than the signal (from the fragment you are monitoring)" I would probably say "filter" instead of "separate" for the ion-optic discrimination during the ion selection but Tom is a chromatographer after all

MIB_EO is refering either to other types of mass spectrometers where you loose more ions during the MS/MS mode or when you ask for a full scan for the second step of the MS selection (instead of just one ion).

[Uwe Neue]

Here is my interpretation:

Two mass spectrometrists meet each other in the hall. One shakes his head and says: "LC? A mess!!!". The other one nods: "Yes, LC - a mess, a mess !!!"

[james little]

Another way to look at increased sensitivity is that the detection limit is a signal/noise ratio. The signal would go down through two mass spec sectors, but the the noise goes down quicker, thus the signal/noise increases.