negative peak before the analyte peak

[Maristela]

Hello

I am working on the detection of a compound in a LC-MS/MS (HPLC1200 - 6410 Agilent MS).
I tested different kind of columns (C18, C8, phenyl) and mobile phases (acetonitrile, methanol, formic acid, ammonium formiate) and I always have a depression before the analyte peak; this depression makes the desired limit of quantitation be deformed. It is like a negative peak, and when the line is going up the peak appears and it seems that the start point of the peak is in the depression of this negative peak.I had already make this study in API 2000 + HPLC 1100 equipment and this does not happen.
Does anybody has an idea ?? I tought it could be something in the HPLC.
Thank you in advance.
Maristela

[lmh]

Are you using SRM already, or just looking at the peak in a TIC or EIC of a standard?

[Maristela]

Thank you very much for the answer.
I am using TIC and the selected transition and the depression appears in all 3 transitions I had selected.

[sassman]

Maybe try MS/MS? You will have all sorts of problems with TIC if your concentrations are low and/or you have a nasty matrix.

[lmh]

If you're using the total ion chromatogram, you are maybe looking at other things besides the analyte of interest. There are probably some background ions that are coming out all the time. A negative peak can happen where something else inhibits the ionisation of the background ion. If the inhibition starts just around where your peak of interest elutes, the background goes down as the peak goes up, and negative "dents" before the main peak can happen, just as you described. It may even be that your target compound is actually the thing that is suppressing ionisation of a background ion. You are quite right, it will give the integrator hell, and give a poor quantification.

Sassman is right, if you make your method more selective, by using SRM, or even in the first instance looking at extracted ion chromatograms for the expected parent mass, things should get better.