Ion suppression in LC-MS and LC-MS/MS refers to reduced detector response, or signal:noise as a manifested effect of competition for ionisation efficiency in the ionisation source, between the analyte(s) of interest and other endogenous or exogenous (e.g. plasticisers extracted from plastic tubes,[1] mobile phase additives) species which have not been removed from the sample matrix during sample preparation.
However, during and after uptake by bioanalytical laboratories worldwide, it became apparent that there were inherent problems with detection of relatively small analyte concentrations in the complex sample matrices associated with biological fluids (e.g. blood and urine).
However, species which are not isobaric may still have an adverse effect on the sensitivity, accuracy and precision of the assay owing to suppression of the ionisation of the analyte of interest.
In APCI, the sole source of ion suppression can be attributed to the change of colligative properties in the solute during evaporization (King et al, J.
ESI has a more complex ionisation mechanism, relying heavily on droplet charge excess and as such there are many more factors to consider when exploring the cause of ion suppression.
[7] Since it is accepted that ion suppression has the potential to affect the other analytical parameters of any assay, a prudent approach to any LC-MS method development should include an evaluation of ion-suppression.
The more comprehensive approach to assessment of ion suppression is to constantly infuse an appropriate concentration into the mobile phase flow, downstream from the analytical column, using a syringe pump and a 'tee union'.
Once the sample has been injected, a drop in signal intensity (or a negative response) should be observed any time a species is ionised in the ion source.
Similar is the effect of reducing the mobile phase flow rate to the nanolitre-per-minute range since, in addition to resulting in improved desolvation, the smaller droplets formed are more tolerant to the presence of non-volatile species in the sample matrix.
In such cases it may be possible to compensate for the effects of ion suppression on accuracy and precision (although not for analytical sensitivity) by adopting complex calibration strategies.
This technique is more robust and effective than using matrix matched standards but is labor-intensive since each sample must be prepared several times to achieve a reliable calibration.
It is important that the internal standard displays very similar (ideally identical) properties, with respect to detector response (i.e. ionisation), as the analyte of interest.
It is important to note that an excessively high concentration of stable isotope internal standard may cause ion suppression itself, since it will co-elute with the analyte of interest.