NLT Theoritical Plate 2000 ?

[metuchem]

Hi everyone,

I have an issiue in my current analytical validation study. One of my impurity does not match with N>2000 but, other SST values and also anayltical paramaters (linearity, precision etc.) are suitable. Are there any way to neglect or to set lower limits for theoritacal plates number? (which is about 1200 in my case)

Thank for answers.

[dap]

Hello.

It is OK if it isn't a dead volume imho.

[mattmullaney]

Hi metuchem,

Short answer is that "it depends" on whether or not you can change the requirement for N. If your firm has no requirement for N, then it seems reasonable to me to change the SST req for your method--but you'll likely need to have a new protocol drawn up to accomplish this properly. There are column types that do not lend themselves to higher plate counts, that is for certain.

What is the retention factor for this particular peak--does it elute early or later in the chromatogram?

For setting a value, I'd inject this substance at the appropriate level multiple times on different days (and different columns) to make the best evaluation.

[metuchem]

Hi mattmullaney,

Thanks for answering

Retention factor is about 2 so it elute too early. I don't have a chance to use different column since it is SB-CN column which we have only one in our laboratory.

Generally we use ICH or FDA guidelines to set limits for these parameters. Both says N>2000 in generally.

My concern is whether should i show additional information to set lower limits for theoritical plates number?

Hi metuchem,

Short answer is that "it depends" on whether or not you can change the requirement for N. If your firm has no requirement for N, then it seems reasonable to me to change the SST req for your method--but you'll likely need to have a new protocol drawn up to accomplish this properly. There are column types that do not lend themselves to higher plate counts, that is for certain.

What is the retention factor for this particular peak--does it elute early or later in the chromatogram?

For setting a value, I'd inject this substance at the appropriate level multiple times on different days (and different columns) to make the best evaluation.

[mattmullaney]

Hi Metuchem,

Your concern is apt on multiple levels.

I said above, " There are column types that do not lend themselves to higher plate counts, that is for certain.

(The peak in question is an early-eluter in the chromatogram--unlucky in this case. I'm assuming that there is little/no extra dead volume in the LC system/LC column. If the retention factor of this peak is 2, the minimum is achieved.)

For setting a (Plate Count N) value, I'd inject this substance at the appropriate level multiple times on different days (and different columns) to make the best evaluation."

Short answer to your last question is "Yes", you will have to validate the value of N for this peak. To do this is not difficult, but you'll require a new protocol, another CN column (at least) and multiple weighments/analyses on different days (at least), preferably with different instruments. The US FDA guideline for N > 2000 from 1994 you refer to (from Nov 1994):

https://www.fda.gov/downloads/Drugs/Gui ... 134409.pdf

on pg. 28 is a Recommendation, not a mandate. If you perform the experiments, show the statistical workup and justify the value you set for the final method, you should be just fine.

[mattmullaney]

Hi Metuchem,

By chance, does your firm commit to a value of N >/= 2000 per HPLC method? I'll hope not. In this case, proceeding will be a bit easier for you.