Analytical assay validation

[vijayassi]

Dear all,

I had a doubt regarding Analytical assay validation , what is the logic behind to do 50% level of Accuracy in assay. pls clarify


Thanks and Regards
kumar

[HPLCaddict]

I share your doubt .
Why do you want to verify accuracy on the 50% level? Is there any guideline specifying this?
AFAIK ICH Q2 only states to have at least 9 preparations of 3 different concentration levels. We usually do 80, 100, 120%, 3 preparations on each level, for plain vanilla assay determinations. If the method is also used for content uniformity, we use 70%, 100%, 130% to cover the complete CU range.
50% level for assay determination is quite senseless IMHO.

[danko]

HPLCaddict is right.
But 50% level could be well founded regardless.
It's all about requirements. If you expect to assay samples that are degraded down to say 70% of target - for instance in stability studies - then 50% level is just adequate.
Så the key message is: Cover the objectives.

Best Regards

[paulw]

I echo what has been said. Perform the accuracy at levels that fit your needs. I can think of at least two instances where I have performed accuracy as low as 50%.

I worked for a period of time at a contract testing laboratory and we performed testing for various companies doing internal compounding (often just dilution) using a number of different technicians. While the final product had to be within a 90-110% range to be considered acceptable for use (where HPLCAddicts 80,100,120 scheme suffices), the customer often wanted to be able to investigate the issues. We found that often the compounding technicians were not the most adept at math (and mass/volume or volume/volume) and often we would see things at either half, or double concentration. To suit our needs we did our accuracy at 50, 100, and 200% so that we could accurately report a true number in these instances without having to do a secondary alternative preparation.

Dissolution studies involving multiple time points and comparision of generic drug vs. name brand may also have to a wider range than 80-120 or 70-130 even as you want to insure the rate of dissolution is comparable and the first few times points can be rather low.