Adding resolution compounds to calibration standard

[KM-USA]

A few years ago, my supervisor insisted that we add resolution compounds (typically fragrance or preservative compounds that are sometimes found in our products fragrance) bracketing the retention time of the API for our cGMP validated HPLC test methods. Supervisor wants us to show that such resolution compounds are resolved from API by more than 1.5, feels it provides a heads up when column resolution decreases, and covers us in an FDA audit by showing compounds in the matrix are resolved appropriately.

Does anyone else work at a company where they intentionally add resolution chemicals to their calibration standards? Thanks.

[danko]

It’s a reasonable requirement to expect some kind of documentation of the claimed separation.
I prefer to cover that by the QC sample which typically is a real life sample comprising both active substance, formulation matrix and finally degradation products.
Some people would argue that the standard for calibration should resemble the unknowns as much as possible ensuring relevant calibration. And I accept that argument as well.
Anyway If you don’t show you’re able to separate the active substance from other compounds you don’t need to do chromatography either. The role of chromatography is to separate

Best Regards

[KM-USA]

I'm dealing with multiple fragrances in a single product type, and those fragrances may keep changing. Most of these fragrance peaks are so small that they're essentially invisible, and may actually be trace components in some of each fragrance's 50 to 100 ingredients, so may change with different production raw materials. The level of the "resolution compounds" is way higher than what would be found in a real life sample, but would be difficult to calculate resolution if such peaks were at the levels found in products.

Maybe the consumer products guy has had experience with this?