Karl Fischer titration coulometric

Karl Fischer titration (coulometric end-point detection)... 

Applications The coulometric Karl Fischer titration is a widely used moisture determination method (from ppm to 100%). In the presence of water, iodine reacts with sulfur dioxide through a redox process, as follows ... 

The water (moisture) content can rapidly and accurately be determined in polymers such as PBT, PA6, PA4.6 and PC via coulometric titration, with detection limits of some 20 ppm. Water produced during heating of PET was determined by Karl Fischer titration [536]. The method can be used for determining very small quantities of water (10p,g-15mg). Certified water standards are available. Karl Fischer titrations are not universal. The method is not applicable in the presence of H2S, mercaptans, sulfides or appreciable amounts of hydroperoxides, and to any compound or mixture which partially reacts under the conditions of the test, to produce water [31]. Compounds that consume or release iodine under the analysis conditions interfere with the determination. 

Distinguish between the volumetric and coulometric methods for the Karl Fischer titration. 

The Karl Fischer titration is a specialised type of coulometric titration. Coloumetry itself is a useful technique, but is not used as a mainstream technique for pharmaceutical analysis. Essentially coulometry is based on the electrolytic reduction of the analyte, i.e. the analyte is reduced by electrons supplied by a source of electrical power and the amount of charge passed in order to convert the analyte to its reduced form is equivalent to the amount of analyte present in solution. 

Figure 17-28 Apparatus tor coulometric Karl Fischer titration.

The Karl Fischer titration,30 which measures traces of water in transformer oil, solvents, foods, polymers, and other substances, is performed half a million times each day.31 The titration is usually performed by delivering titrant from an automated buret or by coulometric generation of titrant. The volumetric procedure tends to be appropriate for larger amounts of water (but can go as low as 1 mg H20) and the coulometric procedure tends to be appropriate for smaller amounts of water. 

Water the Aquatest I does a coulometric Karl Fischer titration of water dissolved in oils. 

Karl Fischer Titration Moisture content of reference standards is commonly and accurately determined by Karl Fischer (KF) titration. KF titration determines total water content, including both the free water and water of hydration trapped in the crystal structure. Coulometric KF-titration is the most sensitive application of the method and is normally used for the small amounts of water found in reference standards. A volumetric technique is available for samples containing large amounts of water. Interference is a relatively common problem in KF titration and thus, due caution must be exercised in the interpretation of KF results. Reagents have been designed to cope with interfering functional groups.48-50... 

For convenient automated laboratory assay, two types of Karl Fischer titration are available the classical, volumetric assay and the more sensitive coulometric assay, which is appropriate for samples containing less than 10 mg of water. In the latter, I2 is generated electrolytically at the cell anode, and the amount of water is determined by the current required for electrolysis. Coulometric assays are useful for compounds that are available in only small quantities, such as compounds in early development. 

With coulometric Karl Fischer titrations, the iodine is generated electrochemically at the anode. This is a much more accurate technique for measuring water content in a sample. Sample sizes are much smaller compared with those for volumetric Karl Fischer titrations. 

Depending on the instrument and the reagents, volumetric Karl Fischer titrations require samples that contain at least 1 mg of water and more typically 5-10 mg. Coulometric titrators require samples with at least 30-50 JLg of water. Considerations of sample availability, solubility, and water amounts will dictate which technique is best for a particular drug substance. A chart to help one decide where to start is shown in Figure 5. 

Adsorption and desorption isotherms may be determined by monitoring equilibrium moisture uptake or loss in samples stored in desiccators with different relative humidities (saturated salt solution yielding different percentage relative humidity). The amount of water present is determined by loss of drying (LOD), TGA, Karl Fischer titration, the coulometric method, or near-IR spectroscopy. 

Hydrates and solvates can be prepared by crystallization in water or an organic solvent or by conversion of the anhydrous material through moisture or solvent adsorption. In quality control testing, hydrates or solvates are identified by the assay of water of crystallization or solvent found in the crystal. Water determination is achieved by Karl Fischer titration or a coulometric method or loss-on-drying by the USP method. In the preformulation study, the hot stage microscope is a useful simple technique. TGA can also be an informative tool, as shown in Figure 15. 

Figure 8 Voltage drop obtained in coulometric Karl Fischer titrations indicating the endpoint.

D4928 Test Method for Water in Crude Oils by Coulometric Karl Fischer Titration ... 

Presently there is available on the market commercial Karl Fischer titration assemblies, some of which automatically stop the titration at the end point Instructions for operation of these devices are provided by the manufacturer and not described herein. This test method is not intended for use with coulometric Karl Fischer titrators. 

Karl Fischer Reagent—Standard commercially available reagents for coulometric Karl Fischer titrations. 

The referee procedure for determination of water in crude oil by coulometric Karl Fischer titration is the mass measurement of the crude oil in 11.1. 

A selection of coulometric titrations of different types is collected in Table 14.2. It may be noted that the Karl Fischer method for determining water was first developed as an amperometric titration procedure (Section 16.35), but modern instrumentation treats it as a coulometric procedure with electrolytic generation of I2. The reagents referred to in the table are generated at a platinum cathode unless otherwise indicated in the Notes. 

Instrumental methods for the determination of water in polymeric materials often rely on heat release of water from the polymer matrix. However, in some cases (e.g. PET) the polymer is hydrolysed and a simple Karl Fischer method is then preferred. Small quantities of water (10 pg-15mg) of water in polymers (e.g. PBT, PA6, PA4.6, PC) can be determined rapidly and accurately by means of a coulometric titration after heating at 50 to 240 °C with a detection limit in the order of 20 ppm. 

Fig. 3.86. Coulometric Karl Fischer water titration (Courtesy of Metrohm). 

In the coulometric version of the instrument, the iodine necessary for reaction is generated electrochemically by applying electrical pulses to the electrode. In this case, a modified Karl Fischer reagent is used which contains iodide instead of iodine. An iodide solution is in contact with the anode in one compartment of the electrolytic cell, which has a diaphragm between the anodic and cathodic regions (Fig. 19.11). Thus, the volume of reagent, which is the indicator in the classical titration method, is replaced by a more precise quantity of current, obtained coulometrieally. 

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