Technical Interviews - How to Prepare For GC Troubleshooting Questions

Similar to my article on how to answer technical questions for pharma for HPLC, we will now look at how to answer troubleshooting questions in pharma in a systematic and methodical way. Make sure that you are also aware of the soft skills that you are implementing along the process. If interested in HPLC troubleshooting, make sure to check that out here.

Troubleshooting in Gas Chromatography (GC) in the pharmaceutical industry involves identifying and resolving issues or errors that may arise during the analysis of pharmaceutical samples. Here's a step-by-step guide to explaining troubleshooting in GC for pharmaceuticals:

Define the Problem

Clearly define the specific issue or error encountered in GC analysis of pharmaceutical samples. This could include peak tailing, poor resolution, baseline noise, retention time shifts, or low sensitivity, among others. The soft skills that you are showing are your ability to reason under pressure. This is particularly important if there is a tight deadline to have a sample analysed.

Gather Information

Collect all relevant information related to the problem. This includes the chromatographic conditions (carrier gas type and flow rate, column type, oven temperature program), sample preparation methods, instrument parameters (detector settings, injection volume), and any observations or symptoms associated with the issue. This is also important because you are saving time over all. If you rush into solving a problem, you may at best not fix the problem or may at worst make it worse. It’s better to gather all of the knowledge that you need first before getting to working on a solution for the issue.

Preliminary Checks

Perform initial checks to ensure the basic setup is correct. Verify that the GC system is properly connected, the gas supply is sufficient, and the instrument is properly powered on and initialised. You may be able to correct the issue without needing to go through the full process. It may be something basic and a quick check will sort out the problem.

Check Chromatographic Conditions

Review the chromatographic conditions and parameters. Verify that the carrier gas is appropriate (e.g., helium or nitrogen), the flow rate is within the recommended range, and the oven temperature program is properly set.

Inspect the Column

Examine the GC column for physical damage or contamination. Check for any signs of degradation, septum or ferrule issues, or column blockages. If necessary, replace or clean the column. This will be an important lesson on equipment maintence.

Sample Preparation

Evaluate the sample preparation method to ensure it is appropriate for the pharmaceutical analytes of interest. Check for possible issues such as incomplete extraction, improper derivatisation, or inappropriate solvent selection.

Detector Issues

If the problem is related to the detector, inspect the detector cell or detector settings. Check for detector gas (if applicable), detector temperature, and detector sensitivity. Verify that the detector response is within the expected range.

Troubleshoot Carrier Gas Problems

If the issue is related to the carrier gas, verify the gas supply, pressure, and purity. Ensure that the carrier gas flow is consistent and free from impurities. Replace or refill gas cylinders if necessary.

Troubleshoot Injection Issues

Evaluate the injection technique and parameters. Check for issues such as overloading, improper syringe or liner, or sample contamination. Optimise injection volume and injection technique for better results.

Calibration and Standards

Verify the accuracy and reliability of the calibration standards used. Ensure that the calibration curve or reference standards are properly prepared, stored, and within their expiration dates.

Systematic Parameter Adjustments

Make small adjustments to various parameters one at a time to isolate the issue. For example, modify the oven temperature program, change the carrier gas flow rate, adjust detector settings, or try a different injection technique. Observe the impact of each adjustment on the chromatography and record the results. This will show your ability of reductive reasoning. You will be showing how you are able to isolate variables and use that to identify the problem.

Data Analysis

Analyse the chromatograms obtained during troubleshooting. Look for any patterns, changes, or anomalies that could help identify the root cause of the problem. Compare the obtained data with previous or expected results to identify any discrepancies. Using current and past data will show how you are able to understand previous patterns. There may be an update to the SOPs needed if this has shown that there has been a consistent problem logged in the past.

Implement Corrective Actions

Based on the analysis of the troubleshooting data, select appropriate corrective actions. This may involve modifying instrument settings, optimising chromatographic conditions, replacing or cleaning components, adjusting sample preparation techniques, or re-evaluating the method parameters. As in point 12, it’s important to make sure that the methods used here are logged so that you can refer back to them again if there is another incident.

Verify and Validate

After implementing the corrective actions, verify the effectiveness by running control samples or reference standards. Ensure that the problem has been resolved and the chromatographic results are satisfactory. Document the troubleshooting process, including the identified problem, steps taken, and the outcome. It would be wise to share this with your team or supervisor so that you can correct this mistake if it were to happen again in the future. This will showcase your ability to work as a team and realise that the collective efforts of the group can help the team as a whole.

Preventive Measures

Take preventive measures to minimise the recurrence of similar issues in the future. This may include routine maintenance of the GC system, regular column conditioning or replacement, using appropriate quality control checks, or updating standard operating procedures.

Remember, troubleshooting in GC for pharmaceuticals requires a systematic approach and attention to detail. It is crucial to document each step of the troubleshooting process for future reference and to ensure reliable and consistent chromatographic results.

If you are someone who is recently graduated and wondering how to best talk about technical skills in a CV/Resume when most of your experience, make sure to check out my article how to do just that here.