Baseline Disturbances

LCMS Troubleshooting Course

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1 - Basics of LCMS Systematic Troubleshooting

2 - Preventive Maintenance Measures

3 - Pressure Issues

4 - No Peaks Detected

5 - Changes in Peak Shape - Part 1

6 - Changes in Peak Shape - Part 2

7 - Ghost Peaks

8 - Peak Area Fluctuations

9 - Baseline Disturbances

10 - Retention Time Fluctuations - Part 1

11 - Retention Time Fluctuations - Part 2

12 - Changes in Chromatographic Resolution

13 - Changes in MS Response

14 - Undesired Fragmentation & Ion Source Settings

15 - Course Summary & Quiz

High Background Signal & Contamination

 Welcome back to the LCMS Troubleshooting Course. This week we are looking at high background signal and how this can impact on our results. High background noise reduces sensitivity and can mask analyte peaks. It often signals contamination, matrix effects, or system cleanliness issues.

Symptoms often include:

Elevated baseline in MS spectra / chromatograms
Persistent background peaks (e.g. plasticisers, solvent additives)

 

Decreased signal-to-noise ratio
Issue Description Solution
Sample / Matrix Effects Sample and / or the sample matrix are often a primary cause of excessive background noise in mass spectrometry due to contamination. Impurities or over concentration can also introduce persistent signals. 
Dilute or re-filter samples
Ensure analyte - compatible matrices
Avoid extreme pH
Mobile Phase Contamination / Deterioration This can be caused by solvent bottles not being sufficiently cleaned out before use, or improper practices such as using parafilm to cover bottles or poor quality solvents. 
Use fresh LCMS grade solvents and additives
Rinse solvent bottles thoroughly to ensure they are clean

 

Replace degraded stocks
Instrument Contamination (Ion Source, Capillary etc) Residues on the ion source, or in the desolvation line can cause noise in the background
Clean the ion source, transfer capillary and optics with suitable solvents.
Run blanks to verify improvement
Column Contamination The HPLC column is also susceptible to contamination. Proper column selection is critical - ensure the column is MS compatible, as not all columns are recommended for use in mass spectrometry. Additionally, other parameters such as temperature, pressure, and pH range must be adhered to when handling chromatographic columns. Additionally, retained matrix compounds can slowly bleed out of the column.
Flush or backflush column
Run a gradient from low to high organic to remove strongly retained compounds from the stationary phase
To exclude the column as the source of contamination, remove it from the flow path and perform a blank test run
Verification Steps  
Run blank injections (no sample)
Compare m/z peaks to known contaminant tables to quickly identify sources
Test solvents alone to rule out solvent contamination
 
 
Contaminated ion source

Fig. 1 Contaminated Ion Source Interface with non-volatile mobile phase additive

That is all for this week. Hopefully, this section has shown the various common sources of contamination within the LCMS and ways to mitigate against these issues. Next week, we shall be covering the large topic of retention time fluctuations and how to combat this issue. 

Your Shimadzu LCMS Team 

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