Assay of drug Product!

[Ammu]

* well ICH says for assay of drug product take 80 to 120% of test concentration...thats is 80% 100% 120% of test concentration and inject them in triplicates.

so whats should be 100% test concentraion.

is it to be taken from linearity calibration curve...or it should be different from this linearity range.

say if my linearity range is 50... 25... 12.5... 6.25...3.125...1.562...0.781 microgram/ml

what should be my 100% test concentration...

How to then calculate the concentration of tablet sample injected from calibration curve regression equation.

Any formula?



* For validation of calibration curve...what three concentration should be choosen for accuracy and for precision separately from calibration curve.

[bert]

100% refers to the theoretical content of drug in the tablet.

regards Bert

[Dan]

Ammu,

The 100% test concentration would be the concentration of the active in your sample solution in your test method. And, as mentioned by Bert, this concentration is based on the 100% theoretical content of the active in the tablet.

So, if you have a tablet that has 100 mg of active (drug) and you prepare one tablet in 100 mL of sample solvent, then your 100% test concentration is 1.0 mg/mL. Your method would have at least one standard that has this same 100% concentration.

I think that you may have things from the ICH a little confused. Here is what the ICH guideline states:
1) The Range for an assay is 80 to 120% of the test concentration.
2) The Range consists of Linearity, Accuracy and Precision.
3) The Linearity must have at least five data points covering the Range.
4) The Accuracy must have at least 9 determinations over 3 concentration ranges covering the Range.
5) The Repeatability (Precision) must have a minimum of 9 determinations covering the Range or a minimum of 6 determinations at the 100% concentration.

Using 1.0 mg/mL as the 100% concentration, an example for your validation would be:

Linearity Standards (usually injected in triplicate):
1.5 (150%) ... 1.2 (120%) ... 1.0 (100%) ... 0.8 (80%) ... 0.5mg/mL (50%)

Accuracy; Spiked Placebos at 3 levels; three preparations each (usually single injection):
120% ... 100% ... 80%

Repeatability:
We use 6 sample preparations at the 100% concentration (single injection per sample preparation)

We normally use 125% and 75% as concentrations for the Range (in the linearity and accuracy) just to be sure we cover the 120-80% that ICH asks for. This is because you may weigh a standard material and get only 118% concentration and that would be too low to meet the 120% ICH value.

The answer to your question about calculating tablet results depends on the calidbration procedure in your method. How do you do your standard preparations? Is there only one standard? or do you use multiple standards?

Regards,
Dan