unstable baseline and baseline drops

Hello all

I am experiencing an unstable baseline problem increasing with increasing MeOH in the gradient and sudden drops in baseline.

This is a typical plasma metabolome profiling experiment with 1290 UHPLC  and 6546 Q-TOF in NEGATIVE ION MODE

A: H20 (0.1 %Acetic acid) B: MeOH ( %0.1 Acetic acid) 

Column ins HSS T3 Xbridge 

As you see this is more like a IR spectra. Nebulizer and system temps are all OK. 

Would incrasing AcA to 1% help?


The gradient program is:

and method parameters are:

Any help and suggestions are much aprreciated.


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