Bioequivalence and Bioavailability Forum

Hello,

The reality is that no matter how much time and money a lab may have, there are limitations during the validation period because one can never test for all OTCs, their metabolites and the excipients. However the latest "incurred samples re-analysis (ISR)" tests that are being done could help as a continuation of the validation. As far as I know, they are done using the validated conditions, which could generate very reproducible results and not show any hidden problems. However, if we were to apply the same general principles employed during troubleshooting (modifications of the mobile phase, different column, different fragment etc) and perform the ISR tests, chances are some potential issues may be uncovered. Repeating a couple of samples from each subject at some strategically chosen time points, using as small of a change as a very shallow gradient which would increase the retention time by, say, 5 times, may take an extra day, but would give more (albeit not total) confidence in the data. I would even go as far as using a different (maybe milder) extraction for high concentration samples, were sensitivity is not an issue. For instance, a simple protein precipitation for samples normally extracted with SPE, especially if the SPE involves the use of solution with very high or very low pH.

Cheers!