Table 3.

Calibration approaches applied when the blank matrix is not available.

Method	Theory or Mechanism	Advantages	Disadvantages	References
Standard addition	It requires that the analyte be spiked in same sample extract at different concentration levels.	Very effective	It requires large sample amount Very time-consuming	[23,67,68]
Background subtraction	The calibration curve is built by subtracting the background.	Useful for biological samples	Low reproducibility Less effective than other methods (lower sensitivity)	[23,66,69,70]
Surrogate matrix	It exploits surrogate matrixes such as neat solvent, stripped and artificial matrixes, that act as a blank-like matrix.	Effective and widely used approach It allows direct and sensitive quantification of analytes	Similar MS signal response of the analyte in both the surrogate and original matrix must be demonstrated	[23,55,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99]
Surrogate analyte method	It requires stable-isotope-labeled standard as a surrogate analyte to allow calibration.	Very effective	Similar MS signal response of both the surrogate and original analyte must be demonstrated The utility of this method is limited by the availability of expensive and pure labeled standards.	[23,72,100]