Hi Jose,

In ESI ion suppression mainly occur when most of the ion current consumed by background substance other than our analyte. So background may be separated by two way, first one is sample preparation, as you say LLE, SPE etc, which is very laborious process and the second one is playing with buffer which is taken with mobile phase. This play most important role for adduct ion formation during ESI. If we chose buffer in such a way that, where our analytes are adducted prominently and background are remain unionized then we can easily short out the problem of ion suppression. In your case you use 0.1% formic acid (FA) as buffer. Probably FA dominantly ionizes background with your analyt. Here you can use 0.01% ammonium formate (AF). Because AF is little bit more softer than FA from the proton donation point of view, therefore probability of background ionization decreases as a result minimize ion suppression. Other wise you can tune method by choosing any other buffer depending upon proton affinity of your analyte.

Hi Jose,

If ion suppresion does not influence desired sensitivity you may ignore it. use isotope labelled internal standard to minimise relative matrix effects (as defined by Matuszewski et al.)

If you need to avoid ion suppression, you may try to:

1. change ionisation source to APCI, which is less susceptible to ion suppression

2. change chromatographic conditions (ACN to MeOH, gradient, longer or different column);

3. monitor phospholipids to optimise chromatography - e.g. Bioanalysis 6(17):2301-16, DOI: 10.4155/bio.14.85

Good luck!

Piotr

Hi Jose,

have you tried HFIP (Hexafluoroisopropanol) instead of formic acid? We use it for analyzing oligonucleotides via LC/MS and we have a very good signal intensity by using this additive. Chromatography is also good.

Article The Role of Fluorinated Alcohols as Mobile Phase Modifiers f...

Regards Markus

Thank you all for the nice replies. I will give them all a try and come back to you. Cheers.