Moisture analysis Karl Fisher method

Water can be identified from its physical properties. Also, trace amounts of water may be determined by Karl-Fischer analysis. The Karl-Fisher reagent is a solution of iodine, sulfur dioxide and pyridine in methanol or methyl cel-losolve. Water of crystallization in hydrates can be measured by TGA and DTA methods. The presence of trace moisture in gases can be determined by mass spectrometry. The characteristic mass ion is 18. 

The analytical method for moisture determination must be validated before use during process validation studies. There are numerous techniques for moisture analysis that range from physical methods, such as loss on drying, to chemical methods, such as Karl Fisher titration. A comparative review of the conventional techniques are presented in an overview [32], The measurement of residual moisture is lyophilized pharmaceuticals by near-infrared (NIR) spectroscopy has recently been expanded [33]. 

In its simplest form, the Karl Fisher titration is a one-point determination of moisture content. The principal advantage is specificity for water. It is also a non-thermal method, which is very sensitive and can be easily automated. The main disadvantage is that the solid must dissolve in the titration medium to be sure that the total amount of moisture is released. If the analysis is carefully designed in such a way that moisture is extracted from the solid to the same degree each time, accurate and reproducible results can be obtained for solids that do not dissolve. 

The influence of sorbed moisture on chemical stability and the flow and compaction of powders and granulations is well established. The moisture content and hygroscopicity of excipients is particularly important as total product processing as well as finished product stability can be affected. Hygroscopicity, moisture-sorption isotherms, and equilibrium moisture content can be determined by thermogravimetric analysis and Karl Fisher titration methods. 

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