quantitation capability of Ion-trap versus Triple Q

[jameslizh]

I am using Agilent LC/MSD trap XCT Plus to quantify compounds (MW<500 Da) via its MRM mode. But the results are not consistent even for the same solution sometimes (have internal standard). I know ion-trap is not an ideal machine for quantatitive analysis, but want to get more clear idea for why. I also want to make sure that such poor consistence is not due to my developed method. Thanks for any comments.

[Slammy1]

The ion trap will let a certain number of ions in, perform a measurement, then move to the next. Obviously, for quantitative analysis a triple quad is superior. You shouldn't expect LC quantitation for MS analysis. You can expect better quantitation by varying injection volume and operating in single-ion monitoring mode on an MS:MS product.

[sindhu]

In Triple Quad systems you can use precursor ion scan, MRM and constant neutral scans which are mainly useful quantifying compounds. The same MS scans are not there in Ion Trap systems.

Thats why Triple Quads are best preferred systems for quantitation.

[lmh]

Traps are quite capable of SRM.

Do check your spray stability. I do not know the Agilent system, but at least with Thermo, and so far as I know with most other manufacturers, traps optimise their filling by doing a quick pre-scan to check on the ions per microsec. If the spray stability is poor, they will get their filling wrong.

I assume your internal standard coelutes exactly and is chemically nearly identical to the analyte? I don't believe methods using an "internal standard" that is sort-of-similar to the analyte and elutes 2min away. It can't compensate for coeluting cosuppressors.

Good luck!

[sassman]

I think one of the problems with doing quantitation on an ion-trap is with dirty matrices. Since the trap has to fill first and then scan ions out, if it is filling up with a bunch of garbage from your matrix you get significant signal suppression relative to a clean standard. A good internal standard can help tremendously, but you are still better off with a triple quad.

However, you should be able to get decent reproducibility with standards. How stable is your signal if you infuse directly bypassing the LC? Are you sure that your problem is not autosampler related?