Chromatography Forum

Hi,

although it is a chromatography forum, I thought this could be something for around the water cooler.

We have perform water determination on an oil based pharmaceutical product. We expect about 0.25% water in the product.
We can use volumetric Karl Fisher, but it seems that this isn't recommended for such a small water content.
Coulometric Karl Fisher seems the way to go, after some searching on the web).

But if we use 5ml of our product, we have 12.5mg water to titrate. Is volumetric Karl Fisher useable in this range, or should we really use Coulometric KF?

Is there a way to justify the volumetric KF?
We found a suitability test by adding know amounts of water to the product, and then perform linearity, and check the intercept with X an Y axis, and everything was within the limits as stated in the test.

Any insights on this non chromatography stuff?


Ace

Our Lab uses 2 gravimetric methods for moisture and volatile matter in oil determination which are Official Methods of the American Oil Chemists Society (AOCS).

Method Ca-2c-25 (Air Oven Method)
Method Ca-2d-25 (Vacuum Oven Method)

Both listed in "Official Methods and Recommended Practices of the AOCS"
6th Edition (2009)

0.25% is not such a low water content, if you use 5mg/mL titrant and you expect 12.5mg of water in 5mL, then you will have a titre of 2.5mL.
If you can show linearity using standard additions, ruggedness by having two analysts perform on different days, and 'everything was within limits as stated in the test' (Compendial method?) then it would appear that you have the basics for validating your method.

Because many of the liquid samples I see are low in water, large volumes are used ( up to 50 ml ), and volumetrically titrated using the 5 mg/ml reagent, although 2 mg/ml would be preferred.

I've found it's easily possible to titrate 1 mg H2O repeatably using 5 mg/mL reagent and a volumetric system, provided the system is dry and at equilibrium.

The critical aspects are ensuring your formulation has nothing that interferes with titration rate ( eg carbonyls, pH extremes ), that it fully dissolves in the solvent, and that you have plenty of solvent in the reservoir. You may only get few sample titrations before you have to change solvent.

You can analyse sample that don't fully dissolve, but protocols have to tightly defined ( stirring time, stirring speed, drift rate, temperature, etc.).

Hi

Just want to add a few things.

Yes you can motivate by above that you want to use volumetric KF instead of coulumetric KF.

A general volumetric titration rule to keep in mind, similar tend to be mentioned in the pharmacopieas: At the specification limit, the volöume needed to titrate the equivalent of the specification limit should be higher than at least 10% of the burette volume. As 10ml tends to be standard 12,5/5=2,5ml which is 25%. Ideally I would try to increase sample volume to 10ml if possible to reach 50% of burrette volume. As you are in the pharma buissness you can check up a formula in USP for calculating "ideal sample weights/volumes". If I find it I will post it.


Edit:

From USP Water <921> method 1a direct titration:

Unless otherwise specified in the individual monograph, use an accurately weighed or measured amount of the specimen under test estimated to contain 2 to 250 mg of water. The amount of water depends on the water equivalency factor of the Reagent and on the method of endpoint determination. In most cases, the minimum amount of specimen, in mg, can be estimated using the formula:
FCV / KF
in which F is the water equivalency factor of the Reagent, in mg per mL; C is the used volume, in percent, of the capacity of the buret; V is the buret volume, in mL; and KF is the limit or reasonable expected water content in the sample, in percent. C is between 30% and 100% for manual titration, and between 10% and 100% for the instrumental method endpoint determination.

Thanks for your replies.
Conclusion: volumetric KF can be justified if needed!

Ace

I am struggling with the same kinda problem how to calculate C..??? can you please replay??? I am using Composite-5 with the 20ml Buret and F=0.5 gm/ml....


Thank you

Thanks for your replies.
Conclusion: volumetric KF can be justified if needed!
Ace

I agree.

Thanks for your replies.
Conclusion: volumetric KF can be justified if needed!

Ace

You would be surprised how low you can go and get good results with volumetric KF if you are careful.

Use Comp 1 or Comp 2 with a 5 mL buret.... That is what I did when I had to measure residual moisture in lyophiles. Could not use coulometric because for solubility reasons I had to use 70% chloroform.

- Karen

Using coulometric KF you could do this on 0.5ml per run, typically. There are KF reagents which are better at dissovling the oil so it doesn't separate out so easily after a number of runs, if this becomees a problem with standard reagents.