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Updated: Aug 4, 2026

Sample Preparation for Probe Electrospray Ionization Mass Spectrometry
Published on: February 19, 2020
A study of ion suppression effects in electrospray ionization from mobile phase additives and solid-phase extracts
Claude R Mallet1, Ziling Lu, Jeff R Mazzeo
1Waters Corporation, 34 Maple St., Milford, MA 01757-3696, USA. claude_mallet@waters.com
Ion suppression in liquid chromatography/tandem mass spectrometry (LC/MS/MS) affects accuracy. Ion exchange cleanup of plasma extracts minimizes this ion suppression/enhancement, improving high-throughput analysis.
Area of Science:
- Analytical Chemistry
- Biochemistry
Background:
- Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is widely adopted for high-throughput analysis.
- Ion suppression/enhancement is a significant challenge impacting quantitation accuracy and precision in LC/MS/MS.
- Existing research attributes ion suppression to endogenous biological materials, but comprehensive optimization for solid-phase extraction (SPE)/LC/MS/MS systems remains underexplored.
Purpose of the Study:
- To describe a straightforward method for quantifying ion suppression/enhancement in SPE/LC/MS/MS.
- To evaluate the impact of various mobile phase additives, ion-pairing agents, and SPE extracts on ion suppression/enhancement.
- To identify optimized conditions for the complete analytical workflow, including extraction, cleanup, separation, and analysis.
Main Methods:
- Development of a simple setup to measure ion suppression/enhancement.
- Comparison of several mobile phase additives, ion-pairing agents, and solid-phase extraction (SPE) extracts against a standard reference.
- Investigation of different cleanup strategies for biological sample extracts.
Main Results:
- The study successfully quantified ion suppression/enhancement across various analytical conditions.
- Results indicated that different mobile phase additives and SPE extracts exhibit varying degrees of ion suppression/enhancement.
- Plasma extracts subjected to ion exchange cleanup demonstrated minimal ion suppression/enhancement for the analyzed compounds.
Conclusions:
- Ion exchange chromatography is an effective cleanup strategy for reducing ion suppression/enhancement in plasma extracts.
- Optimizing the entire SPE/LC/MS/MS workflow, particularly the cleanup step, is crucial for accurate and precise quantitation.
- The developed setup provides a valuable tool for monitoring and optimizing analytical methods to mitigate ion suppression/enhancement.
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