water content for biopharmaceuticals

[miro2009]

Hello readers,
I was wondering what is the optimum way and device setup to be used for "micro" water content measurement for a lyophilized biopharmaceutical product, that is very hygroscopic? We have no experience with karl fischer titration devices, so are there different models with different sensitivity levels?
We want to use minimum number of pooled vials to avoid excessive exposure to atmosphere during vial opening, emptying and weighing (silica used in weighing area), and our water content per vial shouldn't exceed 0.6 mg, so are there recommended models for "micro-determination" as referred to in the pharmacopea?

Your help and comments are highly appreciated.

[tom jupille]

GC with headspace sampling?

[krickos]

If you refer to like chapter 921 of USP i think you mean something like a coulumeter from for example Metrohm AG.

If you do not have a controlled enviroment around, one might consider placing instrument in glovebox equipped with inert gas stream.

[Markus Laeubli, Metrohm]

Dear Miro2009

This really sounds like THE Karl Fischer coulometry application. The coulometric approach allows to analyse very small amounts of water. In your case it should be absolutely no Problem to determine the amount of water in one vial.
Depending of the thermal stability of the substance you add the pharmaceutical to the determination solution or you heat out the water content. There are a lot of applications around.

Do not hesitate to contact your local Metrohm represenative.

[Karen01]

This really sounds like THE Karl Fischer coulometry application. The coulometric approach allows to analyse very small amounts of water. In your case it should be absolutely no Problem to determine the amount of water in one vial.

I agree that coulometric Karl Fischer would be fine for residual water post lyo from a single..

BTW I developed a volumetric Karl Fischer assay for lyophilized drug product in a single vial... I could not do coulometric because I had to use a relatively high concentration of chloroform to dissolve the encapsulating microparticle. I used Comp 1 . Handling was a bit tricky to figure out IN THIS CASE but once worked out the assay was robust.

- Karen