Water Karl Fisher determination

Determination of water of different materials is one of the important tasks of the analytical chemistry. For water determination in organic solvents physical-chemical methods use side by side with the classic titration method by Karl Fisher. In particular, gas chromatography (GC), distinguished its universality and selectivity, is used. However, GC usually used for determination of relatively large quantity of water. 

Water can be identified from its physical properties. Also, trace amounts of water may be determined by Karl-Fischer analysis. The Karl-Fisher reagent is a solution of iodine, sulfur dioxide and pyridine in methanol or methyl cel-losolve. Water of crystallization in hydrates can be measured by TGA and DTA methods. The presence of trace moisture in gases can be determined by mass spectrometry. The characteristic mass ion is 18. 

There are three ways to obtain the total solid (1) determine the water content by Karl Fisher titration, (2) weigh an evaporate portion of product, or (3) sum up all the ingredients, including mometasone furoate and phenylethyl alcohol, which are stated (claimed) on the label. The combination of all three measurements generally gives quite an accurate estimation of the total solid and total cellulose ... 

The Karl Fisher titration is one of the most common and most sensitive methods used in the analytical laboratory. The titrimetric determination of water is based on the quantitative reaction of water with an anhydrous solution of sulfur dioxide and iodine in the presence of a buffer that reacts with hydrogen ions. This titration is a two-stage process ... 

There are two types of Karl Fisher titrations volumetric and coulometric. Volumetric titration is used to determine relatively large amounts of water (1 to 100. ig) and can be performed using the single- or two-component system. Most commercially available titrators make use of the one-component titrant, which can be purchased in two strengths 2 mg of water per milliliter of titrant and the 5 mg of water per milliliter of titrant. The choice of concentration is dependent on the amount of water in the sample and any sample size limitations. In both cases, the sample is typically dissolved in a methanol solution. The iodine/SCVpyridine (imidazole) required for the reaction is titrated into the sample solution either manually or automatically. The reaction endpoint is generally detected bivoltametrically. 

The performance verification of Karl Fisher apparatus should include checks for the accuracy and precision of the instrument. The linearity of the instrument should be determined at installation. The first step is to standardize the instrument (see Section 14.3.2) pure water is sufficient for this purpose. Sodium tartrate dihydrate standard (water content 15.66 0.05%) can be used to assess the accuracy, precision, and linearity of the instrument. Typically, one would measure the water content of at least five samples, over the intended instrument user range. For example, the water content of sodium tartrate dihydrate samples that were 65 mg (ca. 10 mg H20), 195 mg (ca. 30 mg H20), 325 mg (ca. 50 mg H20), 455 mg (ca. 70 mg H20), and 650 mg (100 mg H20) could be determined. Calculate the percent water to assess the instrument s accuracy. The results should be within 98 to 102% of 15.66% water. Determine the % RSD of the percent water found to assess the precision of the instrument. The % RSD should be less than or equal to 1%. Finally, plot the expected water content versus the percent water content to assess the linearity of the instrument s response. A correlation coefficient (r) value of 0.999 or greater is acceptable. 

Air drying at 105°C or vacuum drying at 70°C for > 18 hr is usually used to determine the solid mass in the sample. The Karl Fisher technique is generally recommended, due to temperature abuse in the oven method. However, the oven method is widely used due to its simplicity and availability in most laboratories. The infrared moisture analyzer may also be used for quick determination of water content although it gives a different value from that obtained by the other two methods. 

Water concentrations in liquid and solid phases were measured by the Karl Fisher method using the Karl Fisher Titrator (Mettler DL 18). Butanol and butyl butyrate were determined by gas chromatography using a 6-ft, 5% DEGS on a Chromosorb WHP, 80/10 mesh column (Hewlett Packard, Palo Alto, CA) and hexanol as internal standard. Acid consumption was monitored by volumetric titration of samples diluted in ethanol employing 0.02 M KOH alcoholic solution and phenolphthalein as pH indicator. Esterification was expressed as molar percent of consumed reactant, according to Eq. 1 ... 

Water Determine as directed for Method la in the Karl Fischer Titrimetric Method under Water Determination, Appendix IIB, using a 100-g sample melted on a hot plate at 60°. Use a syringe to apply the oil to the Karl Fisher titrimetric apparatus (usually 1.0 mL is sufficient, but this may vary depending on the water content of the sample). 

Methods of Analysis. Water Content of Fractions. A chromatographic method was employed using a glass column (6 ft x 0.2 mm ID) packed with Po-rapak QS. The chromatographs used were a Varian 3700 or a Hewlett Packard 5880. Water contents were also determined by the Karl Fisher method by Huffman Laboratories, Golden, Colorado. 

It has been proved in several research papers that water is the most important factor in the component s degradation of ORSs. To proceed with the study, the pharmaceutical formulation was prepared by a pharmaceutical manufacture. The batch was packed in six types of packaging material. After storage of samples for 36 weeks maintained at ambient temperature, at ambient temperature and 76% relative humidity, and at 40°C with 80% relative humidity, analyses of water determination were made at different intervals of time. Water determination was performed by loss on drying at 50°C and Karl Fisher methods. 

The submitters used reagent grade tetrahydrofuran (EM Science) dried over 4 A or 5 A molecular sieves (Aldrich Chemical Company, Inc.), and determined the water content in the solvents by Karl Fisher titration (KF). The submitters report that the tetrahydrofuran should be dry (KF < 50 pg/mL) and MUST NOT contain any DMF (< 1 ppm). Also, the KF of the tetrahydrofuran/proline suspension should be < 50 pg/mL. The submitters used (S)-proline obtained from Ajinomoto while the checkers used (S)-proline from Aldrich Chemical Company, Inc. The proline should be milled and/or delumped prior to use, if necessary, to insure complete reaction. The enantiomeric purity of the (S)-proline should be > 99.5%, and can be assayed via the procedure of Marfey.2 The checkers used HPLC grade THF (Fisher Scientific Company) that was dried over 4 A molecular sieves. 

Materials. Sulfolane (99%purity) (Aldrich) was treated with calcium hydride and distilled under reduced pressure. The freshly prepared solvent had a specific conductivity of 1.0 X 10 7 O"1 cm"1 and a residual water content of 8 X 10"3M as determined by Karl Fisher titration. Conductivity water and reagent grade ether (Baker) were used. Glacial acetic acid (CIL), trifluoroacetic acid (Baker), and trifluoro-methanesulfonic acid (3M) were used as received. All these acids had a minimum purity of 99.5% as determined by titration with standard sodium hydroxide. Methanesulfonic acid (Eastman), distilled under reduced pressure, had a purity of 99.6%. Sulfolane solutions of these acids were prepared by weight, and the acid concentrations were checked by acidimetry after the samples were flooded with water. The solutions... 

Analytical Procedures. Standard methods for analysis of food-grade adipic acid are described in the Food Chemicals Codex (see Refs, in Table 8). Classical methods are used for assay (titration), trace metals (As, heavy metals as Pb), and total ash. Water is determined by Karl-Fisher titration of a methanol solution of the acid. Determination of color in methanol solution (APHA, Hazen equivalent, max. 10), as well as iron and other metals, are also described elsewhere (175). Other analyses frequently are required for resin-grade acid. For example, hydrolyzable nitrogen (NH3, amides, nitriles, etc) is determined by distillation of ammonia from an alkaline solution. Reducible nitrogen (nitrates and nitroorganics) may then be determined by adding DeVarda s alloy and continuing the distillation. Hydrocarbon oil contaminants may be determined by ir analysis of halocarbon extracts of alkaline solutions of the acid. 

Materials. The surfactant sodium dodecyl sulfate (SDS) from BDH Chemical Ltd., Poole, England, was twice recrystallized from absolute ethanol. The cosurfactant, pentanol, the methanol, the salt, sodium chloride and the Karl Fisher reagent, which was used for water determination, were all from Fisher Scientific Company and certified. The hydrocarbon, t-butylbenzene, with purity of 99% was from Aldrich Chemical Company, Inc. All of those were used without further purification. Twice distilled water was used. 

In its simplest form, the Karl Fisher titration is a one-point determination of moisture content. The principal advantage is specificity for water. It is also a non-thermal method, which is very sensitive and can be easily automated. The main disadvantage is that the solid must dissolve in the titration medium to be sure that the total amount of moisture is released. If the analysis is carefully designed in such a way that moisture is extracted from the solid to the same degree each time, accurate and reproducible results can be obtained for solids that do not dissolve. 

The stability and suitability of the formulations also needs to be determined, for example, whether the viscosity of the formulation is suitable for the administration route and is stable over time. The water content is a parameter that often has a direct influence on the stability of solid formulations and may influence the appearance of freeze-dried products immensely. Karl-Fisher titration, thermogravitometric analysis (TGA), or DSC is normally used to determine the water content. Various microscopic techniques, where both macroscopic and microscopic appearance of formulation can be determined, such as particle appearance by scanning electron microscopy (SEM) or transmission electron microscopy (TEM), are usually only needed for special formulation. There are several other methods, but which one to choose depends entirely on the formulation and the critical parameters (149,150). 

Follow-up characterization of the volatiles initially analyzed by TGA could also be conducted. Confirmation of the volatiles may be accomplished using one of several techniques thermogravimetric-infrared (TG-IR) spectroscopy, gas chromatography (GC), or thermogravimetry-mass spectrometry (TG-MS). These techniques may be able to qualitatively and quantitatively determine the content and identification of the solvents present in the material. Additionally, Karl Fisher titrimetric assays may be utilized to quantitate the water content in the material. 

Thermogravimetry measures the weight change of a sample as a function of temperature. A total volatile content of the sample is obtained, but no information on the identity of the evolved gas is provided. The evolved gas must be identified by other methods, such as gas chromatography, Karl Fisher titration (specifically to measure water), TG-mass spectroscopy, or TG-infrared spectroscopy. The temperature of the volatilization and the presence of steps in the TG curve can provide information on how tightly water or solvent is held in the lattice. If the temperature of the TG volatilization is similar to an endothermic peak in the DSC, the DSC peak is likely due or partially due to volatilization. It is usually necessary to utilize multiple techniques to determine if more than one thermal event is responsible for a given DSC peak. 

Benzene (analytical grade) was dried by molecular sieves of 4A size and distillated. N-Polyamine (Aldrich, 98%) was double distillated under vacuum. Purity of the reagents was checked chromatographically. It was 99.95 % for CH3(CH2)2NH2 and 99.98% for C6H6. The content of water was determined by Karl Fisher method It was not greater than 0.01%. 

Numerous methods for the determination of monomer purity, including procedures for the determination of saponification equivalent and bromine number, specific gravity, refractive index, and color, are available from manufacturers (68—70). Concentrations of minor components are determined by iodimetry or colorimetry for HQ or MEHQ, by the Karl-Fisher method for water, and by turbidity measurements for trace amounts of polymer. 

Water was determined by coulometric Karl Fisher titration using Metrohm 684 KF Goniometer filled with Aquastar coulomat single solution. 

The extraction of phosphates from freshly cut plants containing different amounts of water at the surface of leaves or within other material could be a source of uncertainty in the analysis step. With this in mind, one solution is to freeze-dry the fresh plant material. The dried material can then be milled to a fine powder, and the content of water is determined by the Karl-Fisher method, as modified by Moibroek and Shahwecker. Finally, analyte anions can be extracted from the plant material in accordance with the AOAC method for dried vegetables and flours. " ... 

Analysis. Free fatty acids were ethylated in ethanol dehydrated with molecular sieves using gaseous HCl as the catalyst. Ethyl esters of fatty acids were analyzed on a DB-23 capillary column (0.25 mm x 30 m J W Scientific, Folsom, CA) connected to a Hewlett-Packard 5890 gas chromatograph (Avondale, PA) as described previously (19). The water content in the oil layer was determined by Karl Fisher titration (moisture meter CA-07 Mitsubishi Chemical, Tokyo, Japan). The contents (by weight) of free fatty acids and fatty acid ethyl esters were analyzed by a thin-layer chromatography/flame ionization detector... 

The Karl Fisher method is recommended for general use in solvents to determine the water eontent. It is not suitable if mercaptans, peroxides, or appreciable quantities of aldehydes and amines are present. Water in halogenated solvents may cause corrosion, spotting, reduce shelf-life of aerosols, or inhibit chemical reactions, thus special method, also based on the Karl Fischer titration, was developed for halogenated solvents. ... 

After purification, quality control of solvent purity is necessary. For this purpose, many different analytical methods are utilized. Generally, chromatographic methods such as GC, GC-MS, and HPLC are used. Moreover, UV, infrared, and nuclear magnetic resonance spectroscopy can also be applied but they tend to be less sensitive toward trace impurities. Water in organic solvents is usually determined by Karl-Fisher titration. On the basis of experimental data obtained before and after purification, the efficiency of the clean-up procedure is determined. In general, the efficiency of purification, e.g., the recovery, is expressed by the coefficient R. This parameter is defined as the ratio of the amount of impurities removed to the amount of solvent before purification ... 

The water content in the as-received powders is determined by the Karl Fisher method and is generally below 0.1%. 

The percentages of water content in cyclohexane and Triton X-45 were measured with titrator ( Mettler Toledo DL38, Karl Fisher Titrator) from Virginia. The particle size and electrophoretic mobility were determined by using zetasizer series nano-ZS, Malvern Instrument from United Kingdom. Stirrer of HTS-1003 LMS was used. 

Moisture. The water content of lecithin products is usually less than 1.0%. As a consequence of lecithin s essentially moisture-free state, lecithins have very low water activity and do not adversely contribute to the microbiological profile of most food systems. Moisture is determined by the Karl Fisher method. A less accurate moisture level can also be determined by azeotropic toluene distillation or drying in an oven at 105 °C. 

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