Changes in MS Response

LCMS Troubleshooting Course

Add Bookmark

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

Welcome Back!

This week, we will be looking at detrimental changes in MS performance, typically relating the MS resolution and mass accuracy. 

1. Drop in Vacuum Readings on the MS

The vacuum is indicative of MS performance and can help to narrow down blockages in the MS. As such, it is important to:

Monitor vacuum readings to gain a pattern

 

Check for vacuum leaks or solvent loss at the interface
If the problem persists, call for an engineer

2. Loss of MS Resolution

MS resolution

Resolution within the mass spectrometer is defined as a measure of it's ability to differentiate between two similar mass-to-charge (m/z) ratios. Different instrument types (i.e. single quadrupole, triple quadrupole, QTOF) will have different resolving power, and as such should not be expected to provide the same sort of structural information. Loss of resolution reduces the separation efficiency and confidence in peak identification, affecting both chromatography and MS performance. 

Symptoms

 Broadened or tailing peaks
 Overlapping analytes
 Deviations in measured m/z (>5 ppm in HRMS)
The first step is to perform and check the tune file. This can often improve the results quickly. 
Quick Tip: After tuning the MS, assess the chromatography for peak shape and retention as many "MS resolution" problems actually originate from LC column performance. 

 

C. Poor Mass Accuracy (HRAM Instruments)

Mass accuracy
Issue Description Solution
Chromatographic Factors
Column degradation or contamination 
Overloading sample volume
Replace or flush column
Reduce injection size or dilute
Mobile Phase Quality
Evaporation or contamination reduces LC performance 
Prepare fresh solvents
Use LCMS dedicated solvents
MS Instrument Drift (Resolution / Accuracy)
Out-of-tune system or contaminated optics 
Re-tune the MS
Clean source
Calibration Issues (HRMS)
Incorrect TOF / Orbitrap calibration
Lock-mass drift (if applicable) 
Recalibrate using standard solutions
Check reference ion and source stability
Detector Saturation
Over concentrated samples saturate the detector 
Dilute sample or reduce injection volume.
Consider using the C13 isotope of the native species to reduce the signal. 

 

Next week will be looking at our penultimate topic - undesirable fragmentation within the MS instrument. We will then have a summary before going on to the quiz for you to assess how much you have learned over the past few weeks.

Your Shimadzu LCMS Team

 

Related Resources