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By Dr Pramod Kumar Pandey - July 8, 2025

Dr Pramod Kumar Pandey BSc (Hons), MSc, PhD, founder of PharmaGuru.co, is a highly experienced Analytical Research Expert with over 31 years in the pharmaceutical industry. He has played a key role in advancing innovation across leading Indian and global pharmaceutical companies. He can be reached at admin@pharmaguru.co

Learn why degassing the mobile phase is essential in HPLC. Discover its impact on system performance, accuracy, and the best degassing methods used in modern labs.”

Why Degassing The Mobile Phase Is Essential In HPLC: Learn In 3 Minutes

Degassing the mobile phase removes dissolved gases such as oxygen, nitrogen, carbon dioxide, etc. from it.

HPLC is a powerful analytical technique used in the pharmaceuticals industry and the mobile phase plays a vital role in it. No matter how sophisticated your HPLC system is, you cannot perform the analysis if you have not degassed the mobile phase.

In this blog, I will discuss why degassing is important, what happens if you skip it, and the common methods used in laboratories today.

Why Do We Degas the Mobile Phase?

Degassing is performed to remove dissolved gases (mainly oxygen, nitrogen, and carbon dioxide) from the mobile phase solvents before they enter the HPLC system. The following steps explain why this is important:

  1. Prevention of Bubble Formation
  2. Improved Detector Sensitivity
  3. Chemical Stability

Chromatogram showing baseline disturbance in the undegassed mobile phase:

Why Degassing The Mobile Phase Is Essential In HPLC
Baseline disturbance in the un-degassed mobile phase

1. Prevention of Bubble Formation

When solvents are pumped under high pressure through the HPLC system, dissolved gases can come out of the solution and form air bubbles. These bubbles can cause:

  • Pressure fluctuations
  • Baseline noise or drift in the detector
  • Inconsistent retention times
  • Potential damage to the pump or detector

2. Improved Detector Sensitivity

Some detectors, especially UV-Vis detectors, are sensitive to oxygen and other gases that absorb light at certain wavelengths. Degassing helps eliminate false peaks and improves the signal-to-noise ratio.

3. Chemical Stability

Dissolved oxygen can react with sensitive analytes or components of the mobile phase, leading to unwanted side reactions. Removing gases helps maintain chemical stability during analysis.

Methods of Degassing

There are several practical ways to degas mobile phases. The following degassing methods are widely usedin the industries:

  1. Vacuum Degassing
  2. Ultrasonication
  3. In-line Degassers
  4. Helium Sparging

1. Vacuum Degassing

The solvent is placed in a vacuum chamber, reducing the pressure so gases escape more readily. This method is widely used and effective for bulk degassing.

2. Ultrasonication

Sound waves agitate the solvent, helping release trapped gas. This method is fast and simple but often used in combination with other techniques for better results.

3. In-line Degassers

Modern HPLC systems often have built-in membrane-based degassers, which continuously remove gases as the mobile phase flows through. These are convenient and provide consistent degassing.

4. Helium Sparging

Helium gas is bubbled through the solvent to displace dissolved air. Since helium is less soluble, it escapes easily, taking the dissolved gases with it. This is one of the most effective methods but can be costly.

Expert Tip:

Among the above degassing procedures,s Ultrasonication and Vacuum Degassing are widely used in industries

What Happens If You Skip Degassing?

Skipping degassing might not always cause immediate system failure, but it can lead to:

  • Noisy or unstable baselines
  • Inaccurate or irreproducible results
  • Unnecessary wear on pumps and detectors
  • Risk of method failure, especially in critical analyses

Expert Tip: Degassing The Mobile Phase

  • During the preparation of the mobile phase, two or more solvents are mixed, and due to this mixing air also dissolves in the mobile phase. N2 (Nitrogen) and O2 (Oxygen) in the air have UV absorption, so they give their respective peaks as noise.
  • Dissolved air can also cause a drop in pressure during analysis.
  • That is why the mobile phase is filtered out during HPLC analysis

Best Practices for Degassing The Mobile Phase

  • Always degass freshly prepared mobile phases.
  • Store degassed solvents in tightly sealed containers to avoid gas reabsorption.
  • Use in-line degassers when running gradient methods or long sequences.
  • For buffer solutions, filter and degass to avoid both particulates and bubbles.

Conclusion

Degassing the mobile phase plays a crucial role in HPLC analysis. Make degassing a routine part of your workflow — your results will thank you!

Related:

  1. Learn HPLC Method Development With Expert Tips, 4 Case Studies and 7 FAQs
  2. Relative Response Factor (RRF) in Pharmaceutical Analysis
  3. Why is the Mobile phase filtered in HPLC: Expert Tips
  4. HPLC Troubleshooting: 5+ Common Problems and Their Solutions

FAQs: Degassing The Mobile Phase

Why is it necessary to degas the mobile phase in HPLC?

Degassing removes dissolved gases like oxygen and nitrogen that can form bubbles under high pressure. These bubbles can disrupt the flow, cause detector noise, baseline instability, and potentially damage the HPLC system. Degassing ensures smoother operation and more reliable results

Can I skip degassing if I’m using an in-line degasser?

In-line degassers are highly effective for routine work, especially with gradient methods, and often eliminate the need for manual degassing. However, for high-sensitivity analyses or when using older systems without built-in degassers, additional degassing (like vacuum or helium sparging) may still be beneficial.

What’s the best method for degassing buffer solutions?

Vacuum filtration, followed by vacuum degassing, is typically the best approach. Ultrasonication alone may not remove all gases effectively from viscous or high-salt buffers. Using in-line degassers with buffer-compatible tubing is also a good option for ongoing runs

How long should I degas the mobile phase?

It depends on the method:

  • Ultrasonication: 5–15 minutes
  • Vacuum degassing: 15–30 minutes
  • Helium sparging: 10–15 minutes
  • In-line degassing: Continuous during operation

Longer times may be needed for more viscous or gas-rich solvents.

5. What happens if a bubble gets into the detector?

Air bubbles in the detector flow cell can cause:

  • Sudden spikes or drops in baseline
  • Increased noise
  • False peaks
  • Detector shutdown or error messages

Further Reading:

  1. LIQUID CHROMATOGRAPHY– MASS SPECTROMETRY: Robert E. Ardrey
  2. HPLC METHODS FORRECENTLY APPROVED PHARMACEUTICALS: George Lunn
  3.  HPLC FOR PHARMACEUTICAL SCIENTISTS: YURI KAZAKEVICH | ROSARIO LOBRUTTO
  4. HPLC analysis
About Dr Pramod Kumar Pandey
Dr Pramod Kumar Pandey

Dr Pramod Kumar Pandey BSc (Hons), MSc, PhD, founder of PharmaGuru.co, is a highly experienced Analytical Research Expert with over 31 years in the pharmaceutical industry. He has played a key role in advancing innovation across leading Indian and global pharmaceutical companies. He can be reached at admin@pharmaguru.co

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