I want everyone to think about this very carefully. When performing an SIR [sic, should be Selected Ion Monitoring (SIM)] analysis using a single ion to characterize an analyte in a matrix free environment (as the poster describes), all the ions of that m/z value will reach the detector, expect for those lost in transmission. In an MRM [sic, should be Selected Reaction Monitoring (SRM)], MS1 is set to allow ions of a single m/z value to reach the collision cell. All ions of that m/z value will reached the collision cell except for those lost due to transmission through MS1.
In the collision cell only a fraction of the ions that enter will produce product ions of the m/z value to which MS2 is set for transmission to the detector. This means that fewer ions representing the analyte are detected in an SRM analysis as compared to an SIM analysis. This is why the peak areas and S/N are worse in SRM than SIM in a matrix free environment.
Where SRM will produce a better limit of quantitation is in the case of matrix interference with the characterizing ion used in the SIM analysis. SRM can have a higher degree of specificity than SIM. This will result in a lower limit of quantitation.
People who categorically say, “SRM is more sensitive than SIM” without stating what the matrix is, are wrong!
