Determination of water in drug substances by Karl Fischer method with water vaporizer

The analytical conditions for the Karl Fischer (KF) method with water vaporizer were studied as routine analysis of water in drug substances. The effects of desiccants for a carrier gas and the heating temperature upon the blank value were examined. It was found that the volume of KF reagent consumed for a sample titration must be corrected using the blank value obtained in the same titration time in all cases. The standard heating temperature for drug substances was investigated by thermal analysis of various compounds with and without containing crystalline water. As the results, 150°C was suitable as the water vaporizing temperature. But, in some cases it was found to heat "10°C below the decomposition point" should be appropriate. The accuracy and analytical precision of this method was enough high compared with those of the direct KF method. Therefore, this method is considered to be useful as the water determination of drug substances which interfere with KF reagents. It is also usable as a simple test method to confirm data obtained by the direct KF method.