causes of ion supression in LC-MS??

[aniket]

Respected Forum,

I just would like to know what are the major causes of ion suppression in LC-MS? Coulb the anticoagulant used for plasma samples be the reason for the ion suppression?? How do you get around this ion suppression??

I would be greatful if all the experets throw some light on this very basic question!!

Thanks,

Keep Smiling!

Aniket

[Mark Tracy]

Ion suppression originates in the charged droplets formed by the electrospray interface. There is only so much charge that a droplet can hold, and all the species are competing for that charge. So if a large concentration of another species co-elutes with one of your drug metabolites, the competition will depress ionization of the target molecule. Another mechanism is if the interfering species forms a strong ion pair that neutralizes the ion of interest; TFA suppresses in this way. The usual anticoagulants are EDTA, citrate and heparin, and they should elute near the void for most RP-HPLC conditions.

[Uwe Neue]

The general approach to get around the problem of ion suppression is a significant reduction in the amount of interferences. The most efficient way to do this is solid-phase extraction, best with a SPE method that is somewhat orthogonal to your analytical method. Common tools are mixed-mode ion-exchangers. You can find well optimized methods and tools at the Waters webside (look for the Oasis applications booklet).

There is actually a very rational behind this. Ion-exchange and reversed-phase separations are orthogonal. If you cut a small slice of the elution pattern from an ion-exchanger, your interferences in reversed-phase are drastically reduced, since this slice is now spread over the entire RP elution window.

[Kostas Petritis]

In addition to the concentration of the interfering compound, it's proton affinity and hydrophobicity will also determine the extend of ion-suppression if any.

For the moment, adequate chromatography or SPE can eliminate the problem, in the future, there is a possibility of eliminating the problem through multiple electrospray emitters (and probably somewhat lower flow rates)...