Analytical Method Validation: Top 5 Interview Questions and Answers

🎙️ The QC Mock Interview

1. The “Why” Question: During Method Validation, why do we perform Specificity before Accuracy or Precision?

2. The Calculation Question: If your column length is 150 mm and your flow rate is 1.0 mL/min, but you switch to a 75 mm column of the same internal diameter, what should your new flow rate be to maintain the same linear velocity?

3. The Compliance Question: If you find that your System Suitability (e.g., %RSD) failed after you already injected 10 samples, can you still use the results of those 10 samples? Why or why not?

4. The Troubleshooting Question: You notice that your peaks are tailing (). Mention two possible chemical causes for this in Reverse Phase HPLC.

5. The LIMS/Data Integrity Question: What is the difference between “Backup” and “Archive” in the context of HPLC electronic raw data?

🟢 Answers (Check your knowledge)

Answer: Because if the method isn’t Specific (meaning it can’t separate the drug from the impurities/excipients), the Area you measure for Accuracy/Precision will be wrong. Specificity proves you are measuring the right thing.
Answer: The flow rate should remain 1.0 mL/min if the Internal Diameter (ID) is the same. Linear velocity depends on the cross-sectional area (diameter), not the length. (However, your run time will be shorter!)
Answer: No. System Suitability is a “gatekeeper.” If it fails, the system was not “suitable” during the analysis, making all data from that sequence invalid. You must investigate, fix the issue, and re-run.
Answer: * Silanol interactions: Basic compounds sticking to acidic silanol groups on the silica.

Column Contamination: Built-up “junk” at the head of the column.
Mass Overload: Injecting a concentration that is too high for the stationary phase to handle.