Bioequivalence and Bioavailability Forum

Hi ElMaestro!

❝ I'd love to be a programmer making new ways to deal with this.

Well, might be nice homework. But PeakFIT comes for just 600$...

❝ Let me ask a broad question here, in relation to one of your points:

❝

❝ When the true T/R is not 1 one could argue that there could (I am not saying there is) be an issue, regardless of whether we talk chromatograms or AUCs.

Or the estimation of λ_z, or AUC_tlast (if t_last,T ≠ t_last,R = the apples-and-oranges-story), or, or, …

❝ I am not aware of this issue being discussed anywhere in the scientific literature, and the bioanalysts I have asked about it also don't have any information.

Well this thread started with the issue of manual integration. In my experience analysts are so scared about findings in an inspection, that they (erroneously) believe manual integration is forbidden data manipulation.* Remember my first example (same study, but low QC sample). Here it is not a question of “perpendicular, tangential, exponential skimmed” integration but simply wrong integration. At T/R=1 of course it would mean out, but for QCs it may lead to rejection - or false acceptance – of a batch. IMHO, bioanalysts should concentrate more on the basics of data evaluation in chromatography rather than blindly accept the results of a silicon-brain. The separation in my example was OK (R_s 2.5) and the tailing pretty good for a chiral method. There is an abundance of literature on the EMG-method. Only analysts can force manufacturers of CDSs to implement better algorithms.

❝ From your example, I would think that above all that the problem with TM is likely to be bigger if we use it in studies to characterise for example the half-life of a new chemical entity or similar.

Yes, if you consider individual samples. But the issue of batch acceptance/rejection is applicable to all studies.

❝ Finally, I solemnly promise I will not make a lengthy post ever again until next time.

Same with me.

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• Dolan JW. Questions from India. LCGC Asia Pacific. 2007;10(1):8–11. free resource.