Select ion monitoring and multiple reaction monitoring (SIM, MRM)

In conventional mass spectrometry, the mass analyser continuously scans a range of m/z values to obtain a full spectrum; however, when there are only a few target ions and their concentrations are extremely low, spending time on irrelevant ions is a waste. Selected ion monitoring (SIM) was developed to address this issue: the quadrupole only allows a few specific mass-to-charge ratios to pass through, blocking all others; this is equivalent to concentrating the entire detection time on the target ions, thereby increasing sensitivity by more than an order of magnitude compared to a full scan.

Multiple reaction monitoring (MRM) is an advanced version of SIM, utilising the geometry of a triple quadrupole (QqQ) system. The first-stage quadrupole selects the parent ion, which is then sent to the collision chamber for fragmentation via CID (see Tandem Mass Spectrometry and Collision-Induced Dissociation), whilst the second-stage quadrupole then allows only a specific characteristic daughter ion to pass through. Ultimately, it is not a single m/z value that is recorded, but rather the ‘parent ion → daughter ion’ ion pair. Double-stage selection reduces background noise to an extremely low level, offering both high sensitivity and specificity; it is the gold standard for trace-level targeted quantification.

The difference between the two can be summarised in a single sentence: SIM is a single-stage screening method that identifies targets based on a single mass-to-charge ratio; MRM is a multi-stage screening method that confirms identity through the combination of parent and daughter ions. When isomeric interference is present or the matrix is extremely complex, MRM offers significantly greater specificity.

Relevance to New Source products: When analysing multi-component systems such as flue gas and reaction gases, the ProC series of online time-of-flight mass spectrometers can perform SIM-style targeted acquisition of several target ions on the list, rapidly identifying nicotine, glycerol, characteristic markers and the like; its MS/MS capability can then be further utilised for MRM-style confirmation, thereby preventing interference peaks from being misidentified as target compounds.

In practice, SIM/MRM requires the prior establishment of a ‘monitoring list’, i.e. the m/z or ion pair corresponding to each target. The more precise the list, the more reliable the quantification; however, too many monitoring channels dilute the sampling points per channel, necessitating a trade-off between the number of channels and temporal resolution.

A typical application is the simultaneous quantification of multiple residues: various pesticides in environmental water samples and pharmacokinetic markers in biological samples can all be analysed in a single run using a single MRM list, thereby eliminating the need for repeated injections. This also applies to the ProC series when analysing multi-component flue gas (see Programmed Temperature Ramp and Online Dynamic Monitoring) – by including nicotine, glycerol and characteristic markers in the monitoring list, stable curve data can be output for each flue gas sample. It should be noted that MRM relies on prior knowledge of parent–daughter ion pairs and is less flexible than full-scan mode for ‘screening for unknowns’; therefore, the standard workflow typically involves first using full-scan mode to identify targets, then switching to MRM for precise quantification, with the two stages complementing one another.