Evaluating Ion Suppression in Method Development

Because of the pervasive and pernicious occurrence of matrix effects, it is usually advisable to build a routine check on the extent of these effects into any method that has been shown to be subject to them, e.g. the ME/RE procedure (Matuszewski 2003) described in Section 5.3.6a. A particularly deceptive cause of ionization suppression that is not really a matrix effect is the mutual interference of an analyte and its co-eluting SIS (Liang 2003 Sojo 2003), discussed in some detail in Section 5.3.6a. While any level of suppression (or enhancement) of ionization efficiency is undesirable, the mutual suppression of analyte and an isotope-labeled SIS appear to be equal, with minimal effect on the validity of the quantitative analysis, although it may adversely affect limits of detection and quantification as a result of the 

It is good practice in the context of checking for matrix effects to conduct regular checks on the response (R and Rjis in Section 8.5) during the course of method development (and also validation, and analysis in a multi-sample run). This can be done in a number of ways but one of the best and most convenient is to simply plot the IS response from beginning to end (recall that it is essentially universal 

Other approaches to alleviating matrix effects that are possible but not often realistic in real-world practical situations include the use of nano-electrospray (Section 5.3.6a) with packed capillary columns, postcolumn splitting so as to deliver flow rates compatible 

Another aspect that is common to matrix interferences (direct contrihutions of matrix components to the signal measured for analyte and/or SIS) and matrix effects (suppression or enhancement of ionization) is that of the consequences of the presence of metabolites or other types of degradates when analyzing incurred analytical samples. Such interferences are in principle absent from the control matrix used for matrix matched calibrators, QC samples etc. Thus use of re-analysis of incurred samples to evaluate and consequent matrix effects was discussed in Section 9.4.7b, and applies equally to matrix interferences arising from presence of metabolites. Variations of metabolite levels among samples (e.g. from different time points in a pharmacokinetic study), which can lead to parallel variations in the extent of both matrix effects and matrix interferences, are an example of how some problems can arise unexpectedly despite prior precantions. 

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