Limits of suspicion, recognition and confirmation as concepts that account for the confirmation transitions at the detection limit for quantification by liquid chromatography-tandem mass spectrometry.

With the emergence of liquid chromatography coupled to tandem quadrupolar mass spectrometry (LC-QqQ) as a routine technique for quantitative analysis, analytical chemists claimed LC-QqQ to be the gold standard to reach the best compromise between versatility, high throughput, robustness, sensitivity and selectivity. In particular, a high selectivity is ensured when two or more transitions are monitored because not only the retention time and protonated molecule are controlled but also two or more product ions are. With the multiple-transition recording, the transition leading to the most intense signal is used for the quantification (quantifier), while the other one(s) is(are) aimed at confirming the detection of the analyte (qualifiers). The confirmation is based on the calculation of the relative intensity between the signal intensities of the quantifier and the qualifier(s). This useful approach raises the question of the validity of the limit of detection (LOD), initially employed for mono-channel detections such as HPLC combined with ultraviolet or fluorescence detection. Furthermore, it was shown that the multiple-transition recording leads to a confusing calculation of the decision limit (CCalpha) and detection capability (CCbeta). In the present article, the LOD is split in three concepts defined as the limit of suspicion (LOS), recognition (LOR), and confirmation (LOC). For these three limits, applications and drawbacks are shown, while determination methods are proposed.