A practical framework for validating high-resolution mass spectrometry for nitrosamine detection in pharmaceuticals, covering regulatory expectations, method setup, calibration strategy, troubleshooting, and compliance.
Core Validation Parameters
Accuracy
Precision
Specificity
Sensitivity (LOD & LOQ)
Robustness
Frequently Asked Questions: HRMS Validation for Nitrosamine Detection
What resolving power is required for nitrosamine analysis?
Why are isotopically labelled internal standards important?
What LOQ is typically required for pharmaceutical nitrosamine testing?
How often should an HRMS method for nitrosamines be revalidated?
Thanks for sharing, Yosuke-San. Isotopically labelled internal standards are always a plus, but at the cost, I do not see them being a QC tool for most situations. Anytime the lab raises the Cost of Goods Sold, there will be discussions well outside of our control.
Technically, one does not need to revalidate the test method. However, we recently found an external lab that could not get any spike recovery. This was after performing the analysis for 3+ years. So, some checks may be warranted.
Sometimes an impure internal standard can yield false-positive results. In order to avoid the recovery issue, one needs to plan a recovery standard solution as part of SST. The mentioned problem will not come in future.
Looks like the framework was adapted from some bioanalytical-related guidance, hence recommendation regarding isotope-labeled ISs, matrix matched calibration etc. which is often redundant for nitrosamines analysis
Some other few points are questionable as well, but overall, the framework can be useful, especially for beginners