RE: RE: RE: RE: Reference Std. Contribution from Ana Madrid written on 6/30/2008 at 13:53
Original contribution: RE: RE: RE: Reference Std. written by Lance Smallshaw on 6/27/2008 at 06:48) Hi Lance, I´m sending some extra information for your comments.
Our objetive is to prepare secondary standards of the impurities of the APIs and APIs we produce. To do so the ICH guidelines indicate that the determination of the content of each substance (its assay result, which in our cases is done by HPLC) must be determined at least by tetraplicate.
Here is where we have a doubt: what should we understand by tetraplicate? Are both of the following options valid? If not what do you suggest?
Option 1:
Get 4 standard vials (each of which is about 5 to 20 micrograms, depending on the substance to be assayed) and dilute them to volumen in order to produce 4 independent standard solutions to be run. (The weigth is declared in the vial as e.g. 5ug, whithout further indications about the precision of the weight in the label of the vial)
Against these 4 replicates of primary standards my 4 replicates of the drug I want to turn into a secondary standard will be run.
Assay scheme (for HPLC runs):
Primary std solution 1 (from vial 1)
Primary std solution 1 (from vial 2)
Primary std solution 1 (from vial 3)
Primary std solution 1 (from vial 4)
Substance to be transformed into Secondary std (solution 1)
Substance to be transformed into Secondary std (solution 2)
Substance to be transformed into Secondary std (solution 3)
Substance to be transformed into Secondary std (solution 4)
Each vial is independent as they only are sold e.g. with 5micrograms of the substance in each.
Each solution of the substance under standarization is prepared independently.
Option 2:
Get 1 standard vial (which is about 5 to 20 micrograms, depending on the substance to be assayed) and dilute it to volumen in order to produce 1 standard solution to be run. (The weigth is declared in the vial as e.g. 5ug, whithout further indications about the precision of the weight in the label of the vial)
Against this solution of the primary standard my 4 replicates of the drug I want to turn into a secondary standard will be run.
Assay scheme (for HPLC runs):
Primary std solution 1 (from vial 1)
Substance to be transformed into Secondary std (solution 1)
Substance to be transformed into Secondary std (solution 2)
Substance to be transformed into Secondary std (solution 3)
Substance to be transformed into Secondary std (solution 4)
Each solution of the substance under standarization is prepared independently.
These questions arose because the cost of the standards is huge, in comparison with our own cost for manufacturing and characterization.
All your comments are very wellcome!!
Thanks again.
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