Water Content Determination by Karl Fischer
Many official drugs contain varying amounts of water either in the form of water of crystallization i.e. hydrates or in absorbed form. Therefore it is important to specify limits of water content in order to maintain some sort of uniformity in these drugs.
Water content can be determined by any one of the following procedures:
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Loss on drying, for drugs containing no constituents other than water volatile at 105°C;
Water content by Karl Fischer (Titrimetric)
Mix and accurately weigh the substance to be tested, and, unless otherwise directed in the individual monograph, conduct the determination on 1 to 2 g. If the test specimen is in the form of large crystals, reduce the particle size to about 2 mm by quickly crushing.
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Tare a glass-stoppered, shallow weighing bottle that has been dried for 30 minutes under the same conditions to be employed in the determination. Put the test specimen in the bottle, replace the cover, and accurately weigh the bottle and the contents. By gentle, sidewise shaking, distribute the test specimen as evenly as practicable to a depth of about 5 mm generally, and not more than 10 mm in the case of bulky materials.
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Place the loaded bottle in the drying chamber, removing the stopper and leaving it also in the chamber. Dry the test specimen at the temperature and for the time specified in the monograph. Upon opening the chamber, close the bottle promptly, and allow it to come to room temperature in a desiccator before weighing.
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If the substance melts at a lower temperature than that specified for the determination of Loss on drying, maintain the bottle with its contents for 1 to 2 hours at a temperature 5° to 10° below the melting temperature, then dry at the specified temperature.
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Water Content by Karl Fischer
The most important method of determination of water content is the Karl Fischer electrometric titration method. It is widely applied for moisture determination of drug substances because it is very rapid, specific and requires a very small amount of sample.
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The method consists of titration of sample in methanol in Karl Fischer reagent which incorporates iodine, sulpher dioxide, pyridine and methanol. The reactions involved are shown as:
Standardization of Karl Fischer reagent
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Place sufficient quantity of methanol in the titration vessel and add sufficient amount of Karl Fischer reagent to give the characteristic endpoint. Weigh accurately 150-350 mg of sodium tartrate, (Na2C4H4O6,2H2O) accurately weighed, by difference and titrate to the endpoint. The water equivalence factor, F in mg of water per ml of the reagent is given by the expression 0.1566 w/v, where w is the weight, in mg, of the sodium tartrate and v is the volume, in ml, of the reagent required.
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The water equivalence factor F, in mgs of H2O per ml of reagent, is calculated according to the formula 0.1566 x w/v, where W is the weight in mgs of sodium tartrate and V is the volume in ml of the reagent.
Each mg of sodium tartrate is equivalent to:
Procedure
Add 30 ml of methanol into titration flask.
Neutralize with Karl Fischer Reagent to the electrometric endpoint.
Refill burette.
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Weigh accurately specified qty of sample and transfer into a titration flask stir for 1 minute and titrate the solution with Karl Fischer reagent to the electrometric endpoint.
Record the volume of Karl Fischer reagent consumed.
