Development of Karl Fischer Reagents

III-3 Pharmaceuticals
2. Pharmaceuticals
The Japanese Pharmacopoeia (7th revision) designates Karl Fischer
methodology as the general testing method for 28 pharmaceutical
products. In addition to volumetric titration, the coulometric titration and
moisture-vaporization methods have also been specified. Normally,
samples are placed in a general-use dehydrated solvent and stirred for
a period before titration. Alternatively, surplus Karl Fischer reagent may
be added to the solution, which is then stirred for a period and reverse
titrated with standard water-methanol. Depending on the solubility of the
sample, a sugar-type or oil-type dehydrated solvent should be used.
The chemical constituents of pharmaceutical products are usually
known so it is possible to determine in advance whether or not a
particular product is suitable for Karl Fischer titration. Coulometric
titration is convenient when only a limited amount of sample can be
obtained (such as when a substance is too valuable to use more than a
few milligrams), or when moisture content is low. The moisture
vaporization method is used when it is difficult to draw the moisture into
the dehydrated solvent, or when interference would occur.
As with other types of substances, the heating temperature must be
selected with care.
Moisture vaporization should be used only after careful consideration.
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Key Points
[Examples of Measurement]
(1) Volumetric titration
Reagents used: Karl Fischer Reagent SS-Z (or SS)
Dehydrated Solvent SU(or MS, FM) 25-50ml