Evaluating Sensitivity and Linearity in Matrix

A possible approach to addressing nonlinearity that is not the result of cross-contributions between analyte and SIS (Section 9.4.5b) is to simply limit the range of reliable response to the linear region. While this is usually defensible with respect to negative deviations at high concentrations where the reasons are more clear-cut and reproducible, it could be problematic at the low end depending on the causes of the nonlinearity there since some of these will be intrinsically irieproducible. If the low end nonlinearity sets in at concentrations close to the desired LLOQ, it is advisable to undertake additional method development work to discover the cause and eliminate it 

Among the experimental variables that might be involved, matrix effects (Section 5.3.6a) are always a possibility. The ruggedness with respect to injection of large sets, and robustness of the calibration curve towards 

ESI/APCI Reached LOD. Matrix effects leading to poor release of analyte 

Ion transport optics Not running in optimum ESI solvent. from droplets (ESI). Running too concentrated (ion detector saturated) 

ESI/APCI Mass Analyzer Dirty optics (not at maximum ion transmission efficiency).  

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