Avoiding LC–MS Signal Suppression


Some practical insights into optimizing LC–MS eluents and parameters to avoid signal suppression.

The following "Ask the Expert" question regarding the suppression of MS signals got the CHROMacademy team thinking. Therefore, we have put together some information on the causes of signal suppression in LC–MS and how to avoid it. 

Members Question:

What is the best alternative to use instead of TFA (0.1%) which suppress MS signal? Analyte: Peptide.


You could try 0.1% formic acid. Making any change to the acid will likely affect the retention of the peptide.


I have tried with 0.1% formic acid but I obtained very bad results with important peaks tailing. Does HFBA (heptafluorobutyric acid) suppress the signal less than TFA?


Any compounds with ion pairing ability are likely to suppress signal in ESI, but this effect is compound dependent. All you can do is give the HFBA a try and see if it gives you an acceptable signal.

Alternatives would be to continue to use TFA, but try negative ion ESI. Positive ion APCI is also a possibility, but you won't get multiple charging so it depends on the mass of your compound vs. the maximum mass for your instrument. Have you tried manually tuning the instrument to see if this improves sensitivity?

If neither of these are options, then you'd need to consider redeveloping your chromatographic conditions using formic.

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