The internal standard responds proportionally to changes in the analyte and provides a similar, but not identical, measurement signal.
[1] Selecting an appropriate internal standard accounts for random and systematic sources of uncertainty that arise during sample preparation or instrument fluctuation.
[1] Ratio plot provides good way of compensation of detector sensitivity variation, but may be biased and should be replaced by Relative concentration/Relative calibration calculations if the reason of response variability is in different mass of analysed sample and traditional (not internal standard) calibration curve of any analyte is not linear through origin.
[1] In gas chromatography-mass spectrometry (GC-MS), deuterated compounds with similar structures to the analyte commonly act as effective internal standards.
[8] However, there are non-deuterated internal standards such as norleucine, which is popular in the analysis of amino acids because it can be separated from accompanying peaks.
[9][10][11] Selecting an internal standard for liquid chromatography-mass spectrometry (LC-MS) depends on the employed ionization method.
[13] Selecting an internal standard in inductively coupled plasma spectroscopy can be difficult, because signals from the sample matrix can overlap with those belonging to the analyte.
[1][14] In Inductively coupled plasma-mass spectrometry (ICP-MS), species with a similar mass to the analyte usually serve as good internal standards, though not in every case.
This includes making adjustments to the sample matrix or instrumentation settings and evaluating whether the selected internal standard is reacting in the same way the analyte is.