Background noise in UPLC-MS/MS experience?

Did anybody experience background noise in UPLC-MS/MS during nitrosamines analysis? Does anybody know how we can reduce it or parameters that play role in increased background noise in such a system? @AmandaGuiraldelli

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Put moisture traps between the gas generator and the LC-MS
Clean your LC-MS interface (ESI, APCI) more often. Use a flow diverter valve before MS to prevent sample to enter the MS.

Hope this helps.


Ashay Mehta
Doctors’ Analytical Labs



There are a lot of causes that need investigation:

1)Make sure LC backpressure is steady;

2)Have you checked the spray shape? An incorrect shape affects the analysis sensitivity;

3)Are drying gas flow and source temperature suitable for solvent flow? A deficient desolvation process compromises the analytical response.

4)Does your equipment have a divert valve? Such a device allows you to switch sample portions to waste before the MS.

Best Regards,

Lucas Maciel


@elenaly Please let us know if those recommendations worked out for you and address the background noise. Thanks @Ashaym and @lucas10mauriz for sharing

Dear all,

Thank you for your valuable help. After more research we concluded that background baseline was due to specific product matrix. So, we proceeded with different sample preparation in order to decrease it. We are even thinking of transferring the analysis from UPLC-MS/MS to GC-MS/MS.

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Hi @elenaly!

You are right… LC-MS is much less tolerant to matrix effect than GC-MS. But in case your target are non-volatile nitrosamines you will need to deal with LC-MS.

Sharing here some ideas:

  1. Depending on the type of matrix you are working you may be injecting matrix compounds that will affect the ionization efficiency of your target nitrosamines, few examples:
  • injection of High Molecular Weight Polymers HMWP (which are commonly incorporated into formulation or as film coating in Extended-Release Tablets) - if this is your case you can change the smp prep. protocol to wash out any HMWP residual
  • If you used a total dissolution protocol (API is totally dissolved in the final diluent), using divert valve to send the LC effluent with API to waste will avoid its deposition in the ionization source which could cause serious matrix effect and sensitivity issues
  • ESI is less tolerant to matrix effect than APCI - Using APCI may be a solution to reduce matrix effect
  1. High background noise contaminants in the eluent can generate a significant baseline of noise
  • use of LC-MS grade solvents helps
  • curious observation: Formation of MeOH, Water and Sodium clusters in ESI(+) increasing the baseline noise
  1. MS system maintenance and cleaning - ideally after each analysis and the frequency maybe even higher if your working with complex matrices that may deposit and stick onto interior parts of MS system or even in LC system (e.g.: deposition of compounds in the switch valve in autosampler)

In case you can share more about the characteristics of the sample you are working would help to have a better idea about which analytical solutions could work best.



hi Amanda,

sorry for not replying to your input earlier.
Thank you for the feedback. It was very helpful indeed.
Our problem seemed to be most likely points 1 & 3. We are in a good way to solve the issue.
Thank you very much.

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