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By Dr Pramod Kumar Pandey - July 4, 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

GC troubleshooting involves identifying and resolving common problems that can affect peak shape, retention time, resolution, sensitivity, and reproducibility GC is a powerful analytical technique used widely in pharmaceutical development and several other industries. However, like any complex instrument, GC systems can experience performance issues that affect accuracy, precision, and efficiency. In this article, I […]

GC Troubleshooting: 7+ Common Problems and Their Solution

GC troubleshooting involves identifying and resolving common problems that can affect peak shape, retention time, resolution, sensitivity, and reproducibility

GC is a powerful analytical technique used widely in pharmaceutical development and several other industries. However, like any complex instrument, GC systems can experience performance issues that affect accuracy, precision, and efficiency. In this article, I will discuss quick identification and resolution of these problems to ensure reliable results and minimise downtime

GC Troubleshooting

The process of identifying common GC problems, their possible causes, and providing practical solutions to these problems to ensure reliable results and minimise downtime is called GC troubleshooting. The following are the common problems of the GC :

  1. No Peaks or Very Small Peaks
  2. Retention Time Shifts
  3. Poor Peak Shape (e.g., Tailing or Fronting)
  4. Baseline Noise or Drift
  5. Split Peaks or Ghost Peaks
  6. Leaky System
  7. High or Low Response (Sensitivity Issues)
  8. Poor Reproducibility
  9. Expert Tip

1. No Peaks or Very Small Peaks

Causes:

  • No sample injected
  • Injector or detector not at the proper temperature
  • The column not installed correctly
  • Leak in the system
  • Detector gases off or insufficient

Solutions:

  • Confirm the sample is being injected (check syringe)
  • Check and stabilise temperatures
  • Ensure proper column installation
  • Perform leak check (e.g., using Snoop or an electronic leak detector)
  • Verify and adjust gas flows

2. Retention Time Shifts

Causes:

  • Inconsistent carrier gas flow or pressure
  • The temperature program is not stable or incorrect
  • Leaks in the system
  • Column degradation or contamination

Solutions:

  • Verify and stabilise flow rates/pressure
  • Calibrate and verify temperature control
  • Check for leaks
  • Replace or trim the column

3. Poor Peak Shape (e.g., Tailing or Fronting)

Causes:

  • Column overload
  • Active sites in the injection port or column
  • Incorrect injection technique
  • Dirty or damaged liner
  • Poor column conditioning

Solutions:

  • Reduce sample concentration
  • Replace or deactivate liner and inlet parts
  • Use split injection for large samples
  • Trim column head (~0.5–1 m)
  • Ensure the column is properly conditioned

4. Baseline Noise or Drift

Causes:

  • Detector contamination
  • Temperature instability
  • Gas impurities (moisture or oxygen)
  • Electronic noise
  • Column bleed

Solutions:

  • Clean or replace detector parts
  • Verify oven and detector temperature stability
  • Use high-purity gases with traps
  • Check electrical connections
  • Use low-bleed columns and proper max temperature

5. Split Peaks or Ghost Peaks

Causes:

  • Poor injection technique (slow injection, syringe problems)
  • Cold spots in the injector
  • Sample degradation or contamination
  • Column void at inlet

Solutions:

  • Use fast, consistent injection
  • Verify the injector temperature is appropriate
  • Use a new, clean syringe
  • Recut the column and reinstall properly
  • Use guard columns to avoid degradation at the inlet

6. Leaky System

Causes:

  • Loose or damaged fittings
  • Worn septum or ferrule
  • Improper column installation

Solutions:

  • Tighten or replace fittings
  • Replace septum and ferrules regularly
  • Reinstall the column using proper torque and technique
  • Perform a leak check after any maintenance

7. High or Low Response (Sensitivity Issues)

Causes:

  • Detector not optimized
  • Sample loss (e.g., due to adsorption or evaporation)
  • Injector liner contamination
  • Dirty or degraded detector components

Solutions:

  • Optimise detector parameters (makeup gas, voltages, etc.)
  • Clean or replace liner
  • Ensure sample vial caps are sealed properly
  • Replace or clean detector components
GC troubleshooting

8. Poor Reproducibility

Causes:

  • Inconsistent injection volume
  • Sample degradation
  • Varying flow or temperature conditions
  • Inconsistent column or liner condition

Solutions:

  • Use an autosampler for consistent injections
  • Store and handle samples carefully
  • Regularly calibrate the flow and temperature
  • Replace consumables periodically (liner, septa, column)

9. Expert Tip

Always condition the GC column for a longer time to avoid general sensitivity and retention time shift issues

Conclusion:

In summary, addressing performance issues in gas chromatography (GC) systems promptly is essential to maintaining accurate, precise, and efficient results in pharmaceutical and industrial applications. Regular maintenance, timely identification of problems, and proper troubleshooting can significantly reduce system downtime and ensure consistent data quality. By staying proactive in monitoring and resolving potential issues, users can maximise the performance and longevity of GC systems, ultimately contributing to more reliable analytical outcomes.

FAQS

What is troubleshooting in gas chromatography?

GC troubleshooting involves identifying and resolving common problems that can affect peak shape, retention time, resolution, sensitivity, and reproducibility

Related

  1. Gas Chromatography (GC) in Drug Development: Techniques, Case Studies, and Expert Tips
  2. Relative Response Factor (RRF) in Pharmaceutical Analysis
  3. What is GC Bleeding And How It Affect GC Analysis
  4. Why GC Capillary Columns Are Preferred Over Packed Columns?
  5. Headspace Gas Chromatography (GCHS): Principle, Procedure, Case Studies and FAQ

Further Reading

  • <621> Chromatography
  • Instrumental Method of Analysis (sixth Edition): williard, Merrit, Dean, Settle
  • Analytical Chemistry: Gary D. Christian
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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