The Karl Fisher titration method was published to determine trace amount of water samples in non-aqueous systems that contained sulfur dioxide. It is currently the standard method used to calculate the moisture content in various products. When looking at titration analysis methods, it can be a challenge to determine which to use. This article takes a look at the difference between coulometric titration vs volumetric titration and provides some recommendations on when to use each. The principle behind the measurement was based on the Bunsen Reaction between iodine (I2) and sulfur dioxide (SO2). German chemist Karl Fischer used a primary alcohol as the solvent, and a base as the buffering agent. Principally, the general chemical reaction takes place: ROH + SO2 + 3 RN + I2 + H2O → (RNH)•SO4 R + 2 (RNH)I In the above reaction, alcohol reacts with SO2 and based to form an intermediate salt, which is then oxidized by the iodine present – water is consumed during this oxidation reaction.
Moisture determination: How is moisture measured?
In alcoholic solvents, water and iodine are consumed in a 1:1 ratio, and in a 2:1 ratio in non-alcoholic solvents. Once the water is completely consumed, the excess iodine is calculated by an indicator electrode in the titrator, indicating the end-point of the titration. The amount of water that was present in the sample is then calculated from the concentration of iodine in the titrating reagent and the amount of reagent consumed in the titration. Typically, the recommended pH range for Karl Fischer titration is 5.5 to 8 for the maximum rate of reaction. For pH levels outside of this range, the titration speed is either significantly slower (values less than 4) or results in a vanishing endpoint (values higher than 8). As such, samples outside of the optimal range should be buffered to reach an overall pH in the recommended range.
Type of Karl Fischer Analyses: Coulometric Titration vs Volumetric Titration
There are two different techniques to determine water content using the Karl Fischer method:
Volumetric Karl Fischer Titration
Water Concentration: 100ppm to 100%
Iodine is added using a burette during titration.
Coulometric Karl Fischer Analysis
Water Concentration: 1ppm to 5%
Iodine is generated electrochemically
Volumetric Karl Fischer Titration
Iodine is added to the sample with solvent, where water is measured by the consumption of Karl Fischer reagent. There are two types of volumetric KF systems:
One Component Reagent
Less expensive and easier to handle, but has a less stable titer, and slower titration speed.
Application: Determining Water Content in Magnesium Aspartate
Water content is a critical parameter for quality control in raw materials and finished pharmaceutical products. In many situations, the potency and effectiveness of the active ingredients in such products may be strongly affected by the water content. Magnesium is crucial in basic cellular function and muscle cell metabolic processes. Both compounds in the application note are used as dietary supplements for magnesium utilization and are found in the form of salts. Water can be present in solid samples such as magnesium aspartate and magnesium gluconate as either surface water, or within cells and capillaries. In order to appropriately determine the water content, suitable sample preparation must be exercised: crushing the sample, dissolving it in high temperatures, or evaporating water in a KF-oven. Proper preparation is needed to ensure water is released completely and dissolved in the alcohol solution. Both volumetric and coulometric Karl Fischer Titration methods can be used, based on the sample water content. The following KF methods have been developed and optimized by Mettler Toledo:
KF Volumetry: Direct titration in methanol: formamide 2:1 v/v, 50 °C
Equipment: V30 Compact KF Volumeter
KF Coulometry: Gas phase extraction T = 180 °C, t = 1800 s, Nitrogen gas
Equipment: C30 Compact KF Coulometer, Stromboli KF Oven Sample Changer
The results, as shown in the table below, shows the deviation of determined water content is not greater than 1%, demonstrating high repeatability. This concludes that both Karl Fischer volumetric and coulometric titration provide accurate results and are recommended to determine the water content of solids. Technique preference – coulometric titration vs volumetric titration – is dependent on sample particle size and water content, as referred.
Marcelo Luftman is the managing director of PROAnalytics LLC, a company dedicated to providing PAT Bioprocessing Solutions. PROAnalytics main areas of expertise include bioreactor probes (biomass, pH, DO, OD, etc.), photometric biochemistry cell culture analyzers, process information management software (PIMS), cell imaging systems, off gas sensors, non-invasive flow sensors, process chillers, and lab analyzers & lab automation systems. PROAnalytics solutions comprise from single analyzers up to complete integrated systems.