How do I identify contamination in my LC-MS system and what should I do?

Maintaining the performance of your LC-MS system is highly important. The main features of success for your system, such as sensitivity, reproducibility, and column life, can be compromised by contaminants.

The ideal scenario for an analysis by LC–MS is where the only things that enter the system are the mobile-phase constituents and additives, and the analyte of interest when it is eluted from the chromatography column. In reality, there are many different ways a contaminant can enter the system and interfere with results.

We put together a few useful steps to follow if you are ever in this situation:

Importance of identifying contaminants

Contaminants can contribute substantially to background ions being detected. Even the slightest addition of ionizable compounds to the mobile phase can increase the background signal and make it quite difficult to detect compounds of interest.

Another important thing to bear in mind regarding contamination is that they can enhance or suppress the ionization of analytes of interest.

Identify the source of contamination

It’s very simple: if you know what the contaminant is, it’s easier to clean and to prevent future contamination.

Some of the most common contaminants are Polyethylene Glycol (PEG) or PEG-Like Materials, Metal ions, Phthalates, Siloxanes, Grease/oils and Surfactants and some of the most common sources for contaminants are Solvents, Samples and LC-MS instrumentation.

Retrace your steps and think where a contaminant might have slipped. To narrow down where the contamination began you can isolate the problem to either the LC or MS system.

How to minimise contaminants

  • Wash columns to mitigate column bleeding
  • Have more effective sample preparation in place, using devices that do not introduce extractable impurities
  • Always use certified mobile phase and minimise filtering of mobile phase solvents
  • Remove any sample components that can interfere with separation, ionization and fragmentation
  • Wear nitrile gloves when handling instrument components and samples
  • Use dedicated solvent bottles for each instrument
  • Use high quality HPLC columns with high matrix tolerance
  • Fully clean column after every use to extend its lifetime


Implementing best practices can be very effective to minimise potential contamination.

For any further information or if you have any questions, give us a call on 0800 030 6896.

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