Metrohm explains Karl Fischer Oven Method

Metrohm's Karl Fischer (KF) Oven Method determines the water content of pharmaceuticals that are not amenable to direct KF titration because they undergo detrimental side reactions, for example.

Water determinations carried out with several pharmaceuticals show that the values obtained with the KF Oven Method all lie within the ranges specified in the European Pharmacopoeia.

The automated KF Oven Technique enhances the sample throughput and repeatability of the results.

The quality and shelf life of active pharmaceutical ingredients depend primarily on the content of adsorbed (surface water) or bound water (water of crystallisation).

Although the fourth edition of the European Pharmacopeia (2002) describes direct KF titration as the most important method for determining water content, in some cases, where substances undergo side reactions with the KF reagents or where they release their water only at high temperatures, the European Pharmacopeia recommends quantification via the loss on drying (LOD) in a drying cabinet or desiccator.

This method also includes all volatile compounds (such as impurities or degradation products) released at higher temperatures.

Depending on the water content of the sample, the KF titration can be performed either volumetrically for higher water contents or coulometrically for lower water contents.

Considering the relatively small amount of water in most pharmaceuticals, samples are analysed coulometrically.

The calculation of the sample's water content also involves the determination of the humidity in the sample vessel and the moisture adhering to the vessel surface, vial cap and septum.

Three empty but sealed sample vials are analysed under the same conditions as the particular sample.

The resulting mean value is stored as a blank value and automatically taken into account in the calculation.

Next, a threefold determination for each compound is performed.

The accuracy of the KF titrations is checked at regular intervals with a certified KF oven standard.

The optimum oven temperature for driving off the water should ensure complete water extraction in a reasonable time, excluding the decomposition of the sample.

This means that the oven temperature should be chosen as high as possible to ensure short determination times, but should still be 20C to 30C below the decomposition temperature.

The oven temperatures for unknown samples are determined on the basis of the water-release curves that were recorded for all investigated pharmaceuticals in the 50-250C temperature range.

In contrast to the range of the recovery rates for the LOD specified by the European Pharmacopoeia (60-120 per cent), the KF Oven Method provides recovery rates between 90 per cent and 110 per cent.

The water content is determined with excellent repeatability in less than 12 minutes, according to the company.

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