Karl Fisher

Water content Karl Fisher (NF T 60-154) or Azeotropic distiilation (NFT 60113)... 

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. 

Moisture has been determined by Karl Fisher moisture titration at 300°C (model Metrohm 756 KF Coulometer with 707 KF oven, available from Brinkmann Instruments, Inc. of Westbury, NY, USA). 

Ethyl lactate was purchased from Aldrich Chemical Company, Inc., and used without further purification. The water content was 0.8 mg/mL by Karl Fisher titration (Metrohm model 684 KF coulometer). 

Tetrahydrofuran was purchased from Fisher Scientific Company and dried over 4 A molecular sieves for 18 hr prior to use. The water content was less than 0.05 mg/mL by Karl Fisher titration. 

Elemental composition In 82.71%, 0 17.29%. Indium trioxide may be digested with nitric acid, diluted appropriately and analyzed for indium by AA or ICP. It may be identified by x-ray diffraction. The oxide may be heated with excess hydrogen and water formed may be analyzed quantitatively by gravimetry or the Karl-Fisher method. 

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. 

The y-form is known to be anhydrous, and contains minimal water. The USP water specification for sorbitol requires that a sample contain less than or equal to 1.0% water in the sample [1]. The thermogravimetry (TG) and Karl Fisher (KF) data for the y-form sorbitol samples analyzed in this study are summarized in Table 4. TG analysis indicated the existence of minimal volatile content in the samples, indicating that the materials were anhydrous. The volatile component was identified as water, based on the KF values obtained for the samples. 

Karl Fisher titrations for H2O on both alcohols prior to usage gave values of <0.01% H2O. Bis (2-ethylhexyl) sodium sulfosuccinate was purum grade obtained from Fluka and received no further... 

Moisture Content Determination by Karl Fisher (KF) Method. 

Small amounts of moisture (up to about 0.5%) in crystalline sugars can be determined chemically by titration with Kad Fisher reagent. A volumetric Karl Fisher titration procedure for moisture in molasses is accepted by AO AC. Automatic Karl Fisher titrators are available, and as acceptance of pyridine-free reagents increases, their use may increase. 

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 ... 

Pyridine was used in the beginning of the development of the method. The reaction was slow and the endpoint unstable because of weak basicity of pyridine. The pyridine system buffers at about pH 4. A stronger base, imidazole, has been used to replace pyridine since it gives a faster response and has the advantages of lower toxicity and decreased odor. The optimal pH range for the SO2 imidazole buffer is at pH 6. It is important that the pH of the Karl Fisher reaction be maintained within the range 5 to 7. Outside this recommended pH range, the endpoint may not be reached. 

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 Karl Fisher instrumentation and its performance verification are discussed in this chapter. The instrumentation, calibration practices, and common difficulties that are encountered are presented. Neither method validation nor method specific problems are discussed. 

Karl Fisher apparatus has to be designed to exclude moisture, deliver titrant, and to detect the endpoint. The air in the system is kept dry with a suitable desiccant,... 

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. 

Chloro-1-pentyne was purchased from Farchan Laboratories. It Is also available from Aldrich Chemical Company, Inc. A freshly opened bottle of cyclohexane contained 16 pg/mL of water (Karl Fisher). If needed, the cyclohexane can be dried over 3A or 4A molecular sieves. 

In contrast to the previous reaction, in this case a single molecule of water reacts with two atoms of iodide. Methylhydrogen sulphite is oxidised to hydrogenosulphate, which is converted in the presence of a base of type RN into an ammonium salt. The Karl Fisher reaction can thus be reformulated as follows ... 

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. 

The effects of moisture content in drug substances iancthed dosage form have been widely studied. Static moisture content can be determined by many methods like Karl Fisher titration, loss on drying (LOD), and TGA. Dynamic hygroscopicity of a drug substance has beerLcWaato four... 

The analytical method for moisture determination must be validated before use during process validation studies. There are numerous techniques for moisture analysis that range from physical methods, such as loss on drying, to chemical methods, such as Karl Fisher titration. A comparative review of the conventional techniques are presented in an overview [32], The measurement of residual moisture is lyophilized pharmaceuticals by near-infrared (NIR) spectroscopy has recently been expanded [33]. 

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 ... 

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