Chromatography Forum

Hi, I was hoping that someone may be able to help me with a query on my current HPLC method validation.
The method being validated is used in order to quantify individual components of a pharmaceutical finished product.
I read that accuracy can be said to be inferred via the completion of the precision, linearity and specificity validation components. At the moment our sop states that we need to complete these three requirements in adition to accuracy but I am begining to wonder if this is actually case. The accuracy component of our method validation is quite tedious and I was hoping that someone may be able to suggest ways in which I can complete the above three requirements in order to allow me to infer accuracy.
Also is spiking a standard of known concentration with the relevent excipients and showing no change to response during the specificity requirement enough to show no interference of my active peaks ?
I hope the above makes sense and I look forward to any replies that may be forthcoming,

Peter

As someone who regularly validates quantitative analytical methods, Not actually performing the accuracy exercise would seem to be very risky. I've not come across anything in the accepted validation guideline texts that allows for the omission of the accuracy exercise.

Using a method for quantitation without investigation of accuracy is IMO a recipe for failure.

Not doing something because it's "tedious" is generally not an option in validation.

In my experience, inferring accuracy from linearity, precision, and specificity results is only applicable to validation of an API method where there is no drug product matrix to spike. In the interests of time you can combine experiments so that method precision and accuracy (and some of linearity) is all done on the same sample set.
Spiking a standard of known concentration with the relevent excipients and showing no change to response seems like a reasonable way to demonstrate specificity although if I was an auditor I would also like to see an injection of excipients alone.

I think you'll still need to do standard additions in order to confirm accuracy through linearity/precision/range experiments. No matter what, you should confirm assay in the matrix against an external standard. We're talking ICH here?

Appreciate this is an old thread but inferring accuracy from precision, linearity and specificity comes straight from the ICH Q2(R1) guidance for both drug substance and drug product (sections 4.1.1 c, 4.1.2 c).

I guess if you strictly follow the ICH, recovery could be assessed as part of method development but could not be included in your validation report if inferred.