Systematic evaluation of the root cause of non‐linearity in liquid chromatography/tandem mass spectrometry bioanalytical assays and strategy to predict and extend the linear standard curve range

In this work, the root cause of the non-linear behavior of the standard curve when using a SIL-IS was investigated and identified. Based on the findings, an improved multiple SRM channels approach was proposed and successfully applied to obtain a linear dynamic range of five orders of magnitude for one test compound. This approach may work particularly well for LC/MS/MS bioanalytical assay of dried blood spot (DBS) samples, for which a direct dilution is cumbersome.