polarity switching issue on Agilent 6495C

Discussions about GC-MS, LC-MS, LC-FTIR, and other "coupled" analytical techniques.

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We are running a 20 minute multi-residue method with almost 500 pesticides on an Agilent 6495C MS and 1290 Infinity II LC system. The method switches between positive and negative mode.

For a while now we have been getting consistently low or no responses for the negative mode compounds, while the positive mode has good response. Running the negative compounds alone, in a method without switching, gives good response. Our technician has replaced the capillary voltage power supply and the high energy diode, neither changed the situation.

Note that we have two other equipment setups of exactly the same type in our lab and neither are experiencing this problem.

We are at a loss for how to continue troubleshooting this. Has anyone seen this before or have any ideas?
When we got our new tq instrument we observed poor signal for a few compounds when running many mrms with polarity switching. The problem was only in a certain mass range and when running multiple mrms, with resulting short inter scan delay times. The service engineer had to spend a lot of time to find the problem but solved it in the end, it was a bad electronic board. They basically tested to replace every board and were able to solve it. Been working great after that. I was glad that we had demo runs from the procurement to compare to so that i noticed the issue and also that our problem was taken seriously by the engineers. Instrument passed comissioning test fine but not our demo method.

Our problem occured when running many mrms in the cycle so I would trouble shoot by running just a few compounds in es+ and es- and see if that works better, to test if there is sn issue with the electronics speed.

When running 500 compounds do you visually review the integrated peaks? I run about 200mrm per injection and peak integration reviewing takes some time but I wont feel confident unless i have seen the integration. Though, internal standard area and RT is quite good indicators of problematic samples.
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