Drying Karl Fischer method

Moisture content. Oven drying. Infrared drying, Karl Fischer method. Near Infrared. 

By this method the weighed dry product is dissolved in methanol and titrated with the Karl Fischer solution until the color changes from brown to yellow. The visual observation can be replaced by an ammeter, which shows an steep increase in current, when the titration is terminated (dead-stop-titration). The samples can be two to four times smaller than for the gravimetric method. To avoid the visual observation completely, iodine can be produced by electrolyzation and the water content is calculated by Coulomb s law. Such an apparatus (e. g. Fig. 1.97.1 and 1.97.2) is available commercially. The smallest amount of water to be detected by such instruments is 10 pg. Wekx and De Kleijn [1.84) showed, how the Karl Fischer method can be used directly in the vial with the dried product. The Karl... 

Dry the sieve and count and examine any particles remaining on the sieve. Brush any particles retained on No 60 sieve onto No 40 sieve. Note if the particles are grit as indicated by their lack of uniformity land a scratching noise when pressing and rubbing the material on a smooth glass slide with.a. smooth steel spatula. Report die number of particles on No 60 sieve and on No 40 sieve 4.4-3.1 Determination of Moisture Use Karl Fischer Method, described in MIL-STD-650 as Method 101.4, with methanol as the special solvent. A detailed description... 

Mill 50% of amoxacillin trihydrate, Saccharin sodium (dried to NMT 2% moisture by Karl Fischer method), and succinic acid through a 100 mesh sieve using Fitzmill or equivalent with blades forward. 

Though the protocol was written for a dry solid, it should also be mentioned that liquid samples can also be run (Firestone, 1998). Liquid samples can be added directly to the vessel itself or can be treated as a solid with an extraction step in the Karl Fischer solvent as presented in the protocol. The preference for moisture analyses is the gravimetric method (unit aj.i) largely due the higher costs of equipment and the use of chemicals in the Karl Fischer method. Currently one observes very few applications of the Karl Fischer method on food products published by the AOAC for nutritional labeling purposes. In particular, these food products are cocoa, cocoa products, confectionery coatings, and molasses (Sullivan and Carpenter, 1993). 

Figure 11.22 shows a typical cyclic voltammogram of ultrapure 1-butyl-T methylpyrrolidinium bis(trifluoromethylsulfonyl)amide ([Pyi,4] TFSA) on Au(lll) [143]. Ultrapurity means that the supplier (in the present case Merck KGaA/EMD) guarantees that water and halide impurities are below the 10 ppm level. Routinely the liquids are dried under vacuum and at elevated temperature to water contents below 3 ppm (the detection limit of the Karl-Fischer method) prior to use in our laboratory. 

Note During the dehydration procedure described in Vol 3, p C399-L, it is required to determine ethanol and water in the cylindrical block removed from the press. In these detns a piece of block (cake) is dried in an oven at 100° to obtain "total volatile content , the water is detd by Karl Fischer Method and then ale is obtd by difference. Finally ether is added to make a colloiding mixture contg 2 parts of ether to 1 part alcohol by wt. The above tests are described in the items which follow... 

The secondary drying will be terminated after the product has reached its final temperature and the desorption rate the desired value. If also RM values determined with the Karl Fischer method are required, three coded vials at a time will be closed with a manipulator parallel to the DR measurements and could be removed (Figure 26). 

Figure 26 Freeze-drying of cytostatica. The high desorption rate value (x) and the scattering of the residual moisture determined with the Karl Fischer method ( ) confirms that the transition phase from main drying to secondary drying was not finished after 22.5 h. The secondary drying could be terminated after 28 h. Product temperature (A).

The methods for the determination of residual moisture currently used at the Center for Biologies Evaluation and Research at the U.S. FDA are the gravimetric (loss on drying) method, the Karl Fischer method, and the thermogravimetric (TG) and thermogravimetric/mass spectrometric (TG/MS) method. Current work in progress involves the use of vapor pressure moisture measurements to provide additional information about residual moisture content and its interaction with the components of the freeze-dried final container and its contents. 

The approved variations [14] in the Karl Fischer method include volumetric titration methods to either a visual (excess iodine or addition of an indicator) or volta-metric endpoint detection method. The visual or voltametric endpoint methods usually require 30-40 mg of sample for analysis for freeze-dried biological products containing from 1.0% to 3.0% residual moisture. Coulometric Karl Fischer instruments generate the iodine from potassium iodide for water titration at the electrodes. Only 10-20 mg of freeze-dried sample is required for accurate analysis. 

The Karl Fischer method may be used in many cases. An extremely sensitive method using tritiated water as tracer for the determination of solvent water content has been developed [268] in which drying efficiency is determined by the addition of a specified amount of tritium-labeled water to a rigorously dried solvent and subsequent determination of the decrease in activity of the solvent after treatment with the drying agent. 

Drying agents, Pearson and Ollerenshaw state that whereas the determination of the water content of solvents by the Karl Fischer method is tedious and requires large samplesi determination by specirophutumetric measurement of the overtone band of water near 5,.3U() cm. is a simple mailer requiring no expenditure of sample. 

This study of methods to determine the moisture content of humic substances has yielded no absolute values for moisture content. The loss on drying shows no end point for water loss and the potential interferences of the Karl Fischer titration prevent definition of absolute values. Certainly, additional research needs to be done in this area. For example, techniques such as NMR and IR might be utilized to define and correlate the moisture status of these substances. In many cases it is sufficient to have a reference point to bring these substances to for comparison purposes. Based on Figure 1, loss on drying at 60°C should be the most consistent reference point, however, the interlaboratory study results showed very poor agreement. Based on this limited study we conclude that the Karl Fischer method gives more consistent results on these samples. 

Water is a contaminant in naphtha and should be measured using the Karl Fischer method (ASTM E-203, ASTM D-1364, ASTM D-1744, ASTM D-4377, ASTM D-4928, ASTM D-6304), by distillation (ASTM D-4006), or by centrifugation (ASTM D-96) and excluded by relevant drying methods. 

The Karl Fischer method is applied in a multitude of substances from finished products (butter, cheese, dried milk sugar, etc.) to solvents and other industrial products (paper, gas, petroleum, plastic films, etc.). Solids and not soluble samples must, prior to the measurement, either be ground into powders, extracted with anhydrous solvents, eliminated as azeotropes or heated to evaporate the water in special accessories. The only difficult cases are encountered with strongly acidic or basic media since they denature reactants as well as ketones and aldehydes which perturb the titration through formation of acetals (special reagents must be used for these instances). 

Since then, two reports have appeared claiming that polymerization of carefully dried TXN cannot be initiated by BF3 complexes alone 56,57). According to Collins, TXN dried over a sodium-potassium alloy to such an extent that the concentration of water is below the detection level of the Karl-Fischer method 57), does not undergo polymerization for 48 hrs in bulk at 70 °C in the presence of 1.25 10-3 mol l-1 BF3 0(n-C4H9)2. This may be due to the low ring strain and low basicity of TXN complexes of BF3 with more basic and more strained oxiranes may open giving zwitter-ions (cf. Sect. 4.2.). However, upon addition of water in concentration comparable to that of the BF3 complex the polymerization of TXN starts. The same result was reported earlier for the solution polymerization in cyclohexane 56). 

Karl Fischer method This is primarily used for low-moisture products and is suitable for determining moisture in dried vegetables and legumes. This sensitive titration method is based on the nonstoichio-metric reaction of water with iodine and sulfur dioxide in pyridine/methanol solution. 

As part of this development work, residual moisture is routinely measured by the Karl Fischer method (in a dry box as recommended by May et al. [13], see Section III.B), with control liquid samples of known moisture, to determine the residual moisture in the freeze-dried material. See Table 3 which shows residual moistures of some of the materials established by ECBS in the year 1999/2000, and Figure 2 which shows the reproducibility and variability of the control liquid of known moisture. 

A minimum of six of the ampoules/vials used for check weighing are marked and numbered at intervals throughout the fill to determine the dry weight (by weighing before filling and after freeze drying and/or further desiccation) of the final material. These samples are used to determine the percentage residual moisture content of the freeze-dried material by the Karl Fischer method. 

Figure 8 dlV and RF (Karl Fischer method) of product A processed with the data of Figure 6 as a function of drying time 1, dfV of the three runs (x, ,A) 2, estimated plot of RF, double arrows maximum and minimum RF measured, horizontal line average of three measurements. 

The most common method for the determination of moisture in botanical materials and dry flavorings is the Karl Fischer. The Karl Fischer method is based on the titration of water in the sample with the Karl Fischer reagents as noted below... 

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