Chromatography Forum

Lately when I run a batch, my ISTD area count drops immediately with patient samples, but not with calibrators or controls. Some compounds drop progressively during the run and others the drop is drastic. Even when I reinject the calibrators as unknowns (not calibrators) at the end of the batch, they are also affected. Service has been cleaning everything (rods, Q1, Q3, collision cell, optics, etc) with no help. I've ruled out different things but we still can't find what the problem is. Does anyone have any suggestions on what's going on with this instrument?

from what you describe it appears your sample prep is not very efficient in removing major matrix components

can you elaborate on the nature of patient samples and what is your sample prep and target analytes?

We’ve been doing the same sample prep for years and never had this issue before. I even ran the same samples on a different LCMS and the run was fine but in the one at the lab still had the issue.
We process urine samples to detect different kind of narcotics.

When cleaning fails, isn't a leak usually the next thing to look for (several times as they can be really hard to find)?

We process urine samples to detect different kind of narcotics.

okay so it should not be that bad indeed
do you only use positive ionization in your method? how about charging (say, there's electronics issue and one of potentials is off or missing)
if working in positive mode only, you could try adding a dummy transition(s) in negative polarity to flush the charge