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

## TL;DR

This paper discusses how cross-signal contributions can cause issues in LC-MS/MS bioanalysis and offers solutions using real-world examples.

## Contribution

The paper introduces a flowchart and case studies to identify and address cross-signal contributions in LC-MS/MS.

## Key findings

- Cross-signal contribution can lead to unexpected peaks in LC-MS/MS assays.
- Seven real-world case studies demonstrate how to identify and solve interference issues.
- A step-by-step flowchart helps narrow down the causes of cross-signal contribution.

## Abstract

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.