We have done the analysis of a standard compound both in positive ionization (PI) and negative ionization (NI) mode with varying concentrations (0.01nanomol-10nanomol). But it seems that the ion intensity is very less so as to observe it. We have even done the analyses in MRM mode, but then the same problem exists. I am wondering whether we can use some chemicals like pentafluropropionic acid, tert-butyl amine, sodium formate or lithium formate for increasing the ion intensity. I just need some valuable suggestions on how to use these chemicals as post-column additives in an ion trap mass spectrometer to improve the ionization. Please provide me the links/research articles on how to use these chemicals for the same.
Thanks in advance
@Trevor : Thank you very much for the suggestion. Indeed we did the analyses using Leu-enk and the instrument is working fine,even the ionization seems to be perfectly alright. We are just trying to create a standard curve using Cyclic-di-GMP and the ionization seems to be ok in negative ionization mode with the mentioned detection limits (0.01nanomol-1 nanomol). We are interested to see more ion intensity values even with lower concentrations. Why we are curious is like even with 10femtomol the ionization seems to be good with Leu Enk !!! Just need to explore it in detail.
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In my different applications by HPLC-MS/MS, I have added formic acid (0.01 to 0.1%) and/or ammonium acetate (0.1mM to 10 mM) to initiate or improve the ionisation phenomenon of my interest compounds in mobile phases (water and/or in MeOH).
Usually, your ion source will be more important factor than mass spectrometer used (e.g. ion-trap versus quadrupole). I guess that you use ESI (electrospray ionization) because this is most popular one. But is still not fully universal source. Maybe (in this specific situation) ESI is not the best choice for your analytes...
You may also want to try LC columns with a more narrow inner diameter, e.g 1 mm or lower. This approach is associated with a higher sensitivity, as the chromatographic band is less diluted when it reaches the ESI-MS. In addition, the lower flow rates that must be used with such columns is well suited for ESI, as smaller electrospray droplets are produced, which is often associated with improved sensitivity.
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