Cross-Signal Contribution as a Challenge in LC-MS/MS Bioanalysis.

Liquid chromatography-tandem mass spectrometry is one of the most sensitive and reliable techniques in the quantitative bioanalysis of small molecules, but it is not free of challenges and traps. This Tutorial focuses on the possible causes of cross-signal contribution, which is often neglected, with seven real-world case studies in which interferences of different origins were identified and related problems were solved. A flowchart is suggested that guides readers step-by-step to narrow down the plausible reasons for the unexpected peaks in their LC-MS/MS assays. The impact of cross-signal contribution on quantitative bioanalysis is also discussed, along with measures that can be undertaken when the phenomenon has been identified.