QTOF Reproducibility

[vichrom]

I'm having some problems with the inter-day reproducibility in the analysis of pesticides by LCMS Q-TOF . I'm using an Agilent 6530 Q-TOF with a 1200 series LC.
The intra-day reproducibility seems fine (%RSD lower than 10%), but when I compare the areas of each analyte between different days they vary too much (sometimes more than 100%).
I've seen this in another method we're working but we've handled it by using internal standard and comparing the relative responses. That way, the inter-day reproducibility is good, but the areas keep oscilating.
The retention times are stable, so I think it is an issue with the mass-spec.
We perform mass-calibration daily and use a reference mass solution during the run to keep a good mass accuracy. During analysis via MassHunter we configure the mass extraction window with the same value for each calibration curve we inject.
Have you experienced a similar issue?
Thanks for your help.

[drewa512]

It is my understanding that quantitative methods on a QTOF are usually plagued with problems with reproducibility. The QTOF is such a powerful tool for unknowns, but in terms of running across multiple days, you will have to deal with drift. I apologize for being vague, but the triple quad is the standard machine for LCMS quantitation.

[vichrom]

Yes, I miss to work on a triple quad.
I've found that the only way to deal with this problem is by using an internal standard.
My question is mainly focused to know if it is an intrinsic problem with TOF instruments, since there are many publications using this instruments for quantitation, even in highly regulated environments.

[Tomtotom]

How do you extract the chromatograms? TOF instrument are affected by changes in temperature. The TOF-tubes expand with rising temperatures, so that the length of the flight path is increased hence your signals in the spectrum are shifted. Chosing the same mass in interday experiments for chromatograms may not always hit the same area of the peak.
If this is the case i would compare the areas by chosing the mass manually.