The KF titration has been the standard method for determining the water content of pharmaceutical ingredients since many years ago. Here is the most important standards which we refer to :

– U.S. Pharmacopeia, USP 25 NF-20, 2002, and USP 26 NF 21, 2003

– European Pharmacopoeia (Pharm.Europe) 4th Edition & Supplements 2002

Both of the standards contain detailed information about the sample size and weight, the titration method (>95% direct volumetric titration), the range of allowed water content and the reagents to be used.

By their nature the given methods are also validated methods; this means that the use of modern, pyridine-free reagents is somewhat severely limited: if modern reagents are used then the methods must be validated by users and it should be proved that the same results are acquired. It is advisable to consult the manufacturer of the reagents in order to avoid any unnecessary work. These remarks apply particularly to Pharm.Europe, which describes the use of a pyridine-containing reagent for KF volumetry that is no longer commercially available , that is the users must prepare it themselves!

But the USP is considerably less restrictive. Although it also describes a pyridine- containing reagent, it however also allows the use of commercially available reagents containing other alcohols than methanol or other solvents or bases than pyridine.

Pharm.Europe describes 442 substances for which the water content has been determined by the Karl Fischer method while the USP describes 285 substances.