Karl Fischer method for determination

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. 

Applications of Karl Fischer Method for Determination of Water in Pharmaceutical Analysis... 

APPLICATIONS OF KARL FISCHER METHOD FOR DETERMINATION OF WATER IN PHARMACEUTICAL ANALYSIS... 

Karl Fischer Method for Determination of Moisture. See under Dynamites in Vol 5, p D1622-L and under Ethanol in Vol 6, p E158-R... 

Figure 19.10—Karl Fischer method for determination of water. The conventional burette titration with visual detection of the end point leads to imprecise results. Thus, a cell containing two small platinum electrodes is used. As long as no iodide is present in the solution, the current between the electrodes is weak. When excess iodide is present in the solution at the instant the equivalence point is reached, a significant current is registered.

The Karl Fischer method for the determination of water is used for prednisolone sodium phosphate as described below. 

The chemical methods of water determination invoke the concepts of direct titration of the water or a chemical reaction between the water and specific reagents that causes the evolution of gases the water is determined by measurement of the volume produced. Chemical methods used for determining moisture also include (1) application of the Karl Fischer method of determining water content, and (2) reaction of quicklime with water in coal and subsequent measurement of the heat generated by the reaction. 

The most common end-point detection method for the Karl Fischer titration for determining water (see Section 20C-5) is the amperometric method with dual polarized electrodes. Several manufacturers offer fully automated instruments for use in performing these titrations. A closely related end-point detection method for Karl Fischer titrations measures the potential difference between two identical electrodes through which a small constant current is passed. 

Natural gas - Determination of water by the Karl Fischer method. Also BS 3156 (10053) Environmental management systems - Specification with guidance for use. Superseded BS 7750 1994 which remains current... 

In almost all theoretical studies of AGf , it is postulated or tacitly understood that when an ion is transferred across the 0/W interface, it strips off solvated molecules completely, and hence the crystal ionic radius is usually employed for the calculation of AGfr°. Although Abraham and Liszi [17], in considering the transfer between mutually saturated solvents, were aware of the effects of hydration of ions in organic solvents in which water is quite soluble (e.g., 1-octanol, 1-pentanol, and methylisobutyl ketone), they concluded that in solvents such as NB andl,2-DCE, the solubility of water is rather small and most ions in the water-saturated solvent exist as unhydrated entities. However, even a water-immiscible organic solvent such as NB dissolves a considerable amount of water (e.g., ca. 170mM H2O in NB). In such a medium, hydrophilic ions such as Li, Na, Ca, Ba, CH, and Br are selectively solvated by water. This phenomenon has become apparent since at least 1968 by solvent extraction studies with the Karl-Fischer method [35 5]. Rais et al. [35] and Iwachido and coworkers [36-39] determined hydration numbers, i.e., the number of coextracted water molecules, for alkali and alkaline earth metal... 

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. 

After prolonged degassing of a large batch of PPG, analyses showed that its hydroxyl, unsaturation, and water contents were 0.97 meq/g, 0.033 meq/g, and 0.0035%, respectively. The hydroxyl content was determined by an acetylation method, carried out with acetic anhydride (10). The amounts of unsaturation and water were determined by the mecuric acetate and Karl Fischer methods (10), respectively. The obtained analytical results indicate that the number-average molecular weight of the dihydroxy material is 2062, provided its molecular weight is arbitrarily assumed to be twice that of the monohydroxy material, and that the mole fraction of the monohydroxy poly (propylene oxide) is 0.066. This value corresponds to a number-average functionality of 1.93 for the PPG. 

Thermogravimetry (TG) is a measure of the thermally induced weight loss of a material as a function of the applied temperature [39], Thermogravimetric analysis is restricted to studies involving either a mass gain or loss, and it is most commonly used to study desolvation processes and compound decomposition. Thermogravimetric analysis is a very useful method for the quantitative determination of the total volatile content of a solid, and it can be used as an adjunct to Karl Fischer titrations for the determination of moisture. 

Ammonium chloride is analyzed by treatment with formaldehyde (neutralized with NaOH) and the product HCl formed is analyzed by titration using an acid-base color indicator such as phenolphthalein. Alternatively, it may be mixed with caustic soda solution and distdled. The distillate may be analyzed for NH3 by titration with H2SO4 or by colorimetric Nesslerization or with an ammonia-selective electrode (APHA, AWWA, WEF. 1995. Standard Methods for the Examination of Water and Wastewater. 19th ed. Washington, DC, American Pubhc Health Association). The presence of ammonia or any other ammonium compound would interfere in the test. The moisture content in NH4CI may be determined by Karl—Fischer method. 

Calibration of Karl Fischer FIA method for determination of residual in water in pharmaceuticals. The analyte was methanol containing 0.05, 0.1, 0.2, 0.4 and 0.5% w/v water. 

In Figure 1.68.2 the influence of shielding the product in vials from the walls and doors is summarized. For each run (a), (b) and (c) six groups of vials (168 vials each) filled with 2.8 cm3 (9 mm thickness) of human albumin product, containing 6% solids, were used. Rows 4, 5 and 6 were close to the door and 1, 2 and 3 close to the back wall the condenser connection was at the bottom of the chamber. The RM were determined by the Karl Fischer method. Figure 1.68.3 shows the program of the tests. 

The authors concluded that water which cannot be removed at 100 °C is bound in such a way that it cannot jeopardize the pharmaceutical product. Only the free water can diffuse from the stopper to the product. The moisture content is measured by the Karl Fischer method with different temperatures in the oven, 100 °C to determine the free water content and up to 300 °C to measure the free and bound water. The authors suggested developing a similar program for other stoppers, since the time for such measurements is relatively short (1 week) instead of observing the RM in a product over long times. Table 1.15.2 summarizes the results with the stoppers described above. Table 1.15.3 lists the limits of the free moisture content in 2 types of stoppers and for different cake weights under the assumption that a maximum RM increase of 0.5% in the product is acceptable. 

Using an Existing Method. This is the easiest of the three method-generation options. An example of this would be the use of a Karl Fischer method developed for moisture determination in DS hydrochloride being used in DS sulfate. Regardless of the apparent suitability, the decided use of an existing method must be confirmed with method-feasibility experiments. 

Some carbohydrate derivatives are too insoluble in benzene to be so esterifled, and, for them, a suitable, alternative solvent is 1,4-dioxane, the water azeotrope of which may, by careful, fractional distillation be removed before the solvent, and the water evolved in the reaction determined, if desired, by the Karl Fischer method. Whereas methyl a-D-glucopyranoside can be esterifled by the benzene procedure, the analogous a-D-mannoside ester must be prepared by use of 1,4-dioxane or by some other variation.3... 

Karl Fischer electrometric titration method for determination of water content (WHO/M/7.R1)... 

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 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. 

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