Resolution value in BE studies [Bioanalytics]

posted by ElMaestro  – Denmark, 2019-01-02 23:32 (836 d 22:32 ago) – Posting: # 19723
Views: 1,745

Hello sera,

» How can the resolution value between analyte of interest and internal standard in the chromatograms for the above study be justified to be appropriate? What is your opinion for the baseline resolution lower limit?

Sounds like you have classical HPLC quantification without MS/MS? If this is not the case, stop reading now :-D

The resolution makes extremely good sense...if the peak is symmetric and even more so if it obeys certain mathematical rules. If the peaks are Gaussian (and there is not the slightest theoretical reason to think any peak is) then the theory behind resolution has a visually appealing significance and results in some fine rules of thumb.

But departure from Gaussianism is difficult to quantify - in theoretical maths you have skewness and curtosis and a palette of asymmetric distributions which all seem to be lacking practical application in the grand scheme of chromatolophystic things. Therefore, the resolution metric quickly loses its significance if the peaks are non-Gaussuan.
So it isn't quite easy to define any practical rules for resolution that fit all cases. When you can clearly see tailing or fronting offset "a lot" from the baseline then calculation of resolution may be ... well.... something you do if or when a regulator asks for it but not because it is something that makes particularly sense.
At the end of the day, if your peaks with or without t or f and so on are separated so much that you can resolve them quantitatively (the area of one peak does not overlap [=confound the area calculation of] the other) then you have a good case regardless of the resolution metric. You just need to convince the powers that be about this mere fact.

I would be inclined to take a practical approach here: If you pass validation and if your study sample chromatograms truly look like (and note, I do not quantify the meaning of this) the validation chromatograms then how could a resolution metric issue really be a problem in your study?

Pass or fail!
ElMaestro

Complete thread:

Activity
 Admin contact
21,419 posts in 4,475 threads, 1,508 registered users;
online 12 (0 registered, 12 guests [including 5 identified bots]).
Forum time: Sunday 23:05 CEST (Europe/Vienna)

Nothing fails like success because you do not learn anything from it.
The only thing we ever learn from is failure.
Success only confirms our superstitions.    Kenneth E. Boulding

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5