Karl-Fischer analysis

To this mixture there is then added slowly over a period of 30 minutes 10 grams of - -)-a-aminobenzylpenicillin beta-naphthalene sulfonate. The mixture is agitated for 3 hours at 25°-30°C. The product, D- -)-o -aminobenzylpenicillin trihydrate precipitates and is collected by filtration. The filter cake of the product is washed several times with methyl isobutyl ketone and is dried at 40°C. The product is obtained in about a 90% yield and has a potency of 865 mcg/mg. It is determined by Karl Fischer analysis to have a moisture content of 13.4% by weight. 

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. 

A round robin study of accuracy and precision of the coulometric procedure identified sources of systematic error.33 In some labs, either the instruments were inaccurate or workers did not measure the quantity of standards accurately. In other cases, the solvent was not appropriate. Commercial reagents are designed for Karl Fischer analysis. Reagents recommended by the instrument manufacturer should be used with each instrument. 

There is the possibility that complexes isolated from aqueous (or aqueous alcoholic) media are not hydroxide adducts, but, instead, hydrated alco-holates. The above adaptation of the Karl Fischer analysis does not, unfortunately, distinguish between a hydroxide ion and a water molecule. Such a distinction could possibly be made by detailed x-ray analysis however, neither alcoholates nor adducts have, as yet, been obtained in a form suitable for such a study. 

Butanediol is specified as 99.5% minimum pure, determined by gas chromatography, solidifying at 19.6°C minimum. Moisture is 0.04% maximum, determined by Karl Fischer analysis (directly or by a toluene azeotrope). 

Water analysis can be routinely carried out by a Karl-Fischer analysis in which the ionic liquid is diluted in methanol before analysis. A spiking approach can be used to produce a calibration curve that allows for background effects. At very low levels of water (<10ppm) quite substantial sample sizes can be needed for this method to be meaningful. 

The water content of the ethanol, determined by Karl Fischer analysis, is 0.02-0.10%. 

Experiments were performed using toluene (Merck, purity > 99.5%), cyclohexane (Fluka, purity >99.5%), naphthalene (Merck, purity >99%), polystyrene (BASF, Mw = 101000 g/mol, Mn = 93000 g/mol) and carbon dioxide (Linde, technical grade, purity > 99.5%). The solvents were dried over molecular sieves. The water content was checked with Karl Fischer analysis. All other materials were used as received. 

Karl Fischer titration. The Karl Fischer analysis should indicate that the solution is completely water-free. If water is present the mixture should be refluxed for an additional hour. 

Another Karl Fischer analysis should then be performed, and if water continues to persist, an additional 0.1-0.2 mole of triethyl orthoformate should be added and the refluxing continued for an additional hour. Upon concentration of the solution to a volume of 11., and then cooling it to 0° under nitrogen to exclude moisture, pastel-green hygroscopic needles of the tetrakis-(ethanol) complex (140 g., 22%f) form. These are collected and carefully dried under nitrogen on a Schlenk frit at 23°. Anal. Calcd. for C8H24C104Ni C, 30.61 H, 7.71 Cl, 22.59 O, 20.39 Ni, 18.70. Found C, 27.71 H, 6.95 Cl, 22.97 O, 20.82 Ni, 19.09. 

Specifications and Analytical Methods, Butanediol is specified as 99.5% minimum pure, determined by gas chromatography (gc), solidifying at 19.6°C minimum. Moisture is 0.04% maximum, determined by Karl-Fischer analysis (directly or of a toluene azeotrope). The color is APHA 5 maximum, and the Hardy color (polyester test) is APHA 200 maximum. The carbonyl number is 0.5 mg KOH/g maximum the acetal content can also be measured directly by gc. 

The hydrotreated base naphtha contained less than 0.5 ppm sulfur. The naphthas were dried over molecular sieve and stored under an inert gas (Ar) prior to use in the pilot unit. Using Karl-Fischer analysis the water content of the dried naphthas was measured to be 5-8 wt ppm. In order to compensate for the effect of the remaining water on the chloride content of the catalyst, 0.8 wt ppm chloride as 1,1,2-trichloroethane was added to the naphthas. Hj (99.995%, Norsk Hydro), supplied from gas cylinders, was passed over a deoxo catalyst (BASF R3-11) at 70°C and a 4A molecular sieve to remove traces of oxygen and water, respectively. The deoxo catalyst as well as the molecular sieve were regenerated between each test run. 

Last and Prebble [51 ] developed a near-infrared reflectance (NIR) method for the determination of moisture in an experimental freeze-dried injection product. NIR spectra were collected through the bases of unopened product vials using a horizontal instrument accessory. The samples in these vials were then used for Karl Fischer analysis to generate a standard curve for the analysis. The NIR data must be correlated with an accepted residual moisture technique in order to yield a meaningful result. This article states that NIR accuracy and precision in this application are not consistent with allowing the use of the current method in anything but a screening role. 

Results from weight-loss measurements were modeled.f Research indicates that the determination of water content by Karl Fischer analysis in effervescent tablets was possible after extraction with diox-ane. NaHCOs, which reacts with the Karl Fischer reagent, is insoluble in dioxane and does not interfere during the determination. 

Spitz, H.D. Determination of water in aluminum chlorohy-drate and effervescent tablets by karl fischer analysis. J. Pharm. Sci. 1979, 68, 122-123. 

Often the easiest way to set the initial water activity of components of the reaction mixture is by pre-equilibration with a saturated salt solution. The relative humidity or water activity is fixed above a saturated solution of a given salt at a known temperature. As water equilibrates in or out of the solution, solid salt will tend to dissolve or crystallize to maintain saturation and hence the fixed water activity in the headspace. Any other material placed in contact with the headspace will eventually equilibrate to the same water activity. The reaction mixture component can simply be placed inside a closed vessel together with the salt solution, such that water can transfer between the two via the vapour phase. Wide-mouth screw cap jars are convenient, with salt solution over the base and an open vial containing the sample (Fig. 8-3). The rate of equilibration depends on the surface areas exposed and the amount of water that must be transferred. Typically 1-2 days is sufficient for either solid biocatalyst preparations or liquid phases based on relatively non-polar organic solvents. The rate of equilibration may be checked by weighing or Karl Fischer analysis respectively. 

In order to elucidate the effect of water absorption on the charge storage behavior of commercial Ultem 1000 films (50 pm thickness Lipp-Terler), samples with various water contents were prepared. The water content was determined by a weight gain method using a Mettler Toledo MX5 micro-balance with a resolution of 1 pg. The water content of as-received films was determined by Karl-Fischer analysis to 0.74 wt%, compared to an equilibrium water absorbance of PEI at 1.39 wt% [27, 74], As a preconditioning step, the specimens were dried under vacuum at 125 °C for 24 h to ensure a water content of less than 0.02%. By additional immersion treatments, the water content of these PEI films was increased to films with 0.45 wt% and 0.66 wt%. 

When the resulting cerium(lll) chloride (730-779 mg) is dissolved in 10 mL of dry methanol, Karl Fischer analysis of the solution shows that the cerium(tll) chloride contains 6.5-7.6% of water which is equal to 95-113% of the water expected from the formula CeCl3-H20. 

During tertiary recovery, the produced fluids were analyzed microscopically for the presence of oil-in-water and water-inoil emulsions. Karl Fischer analysis was performed on the produced fluid samples in order to determine the amount of oil present in the aqueous phase and the amount of water present in the oil phase. Also pH readings were recorded for the produced aqueous phase throughout tertiary recovery. 

Care must be taken to ensure that the sample is not exposed to environmental moisture prior to analysis. Karl Fischer analysis must be one of the first tests to be performed on stability samples when the container is first opened. If the sample is not solution in solvent, additives may be used to assist with sample solubility. 

Under industrial conditions the moisture present in material must be determined by faster methods, such as by electrical methods of which three main varieties have become widespread moisture determination based on the change of the ohmic dc resistance, a measurement of the electrostatic capacitance (dielectric constant of the material), and a measurement of the loss in an ac field. Other quick methods are the chemical methods developed mainly for the most frequently occurring case, when the moisture is water, such as the Karl-Fischer analysis based on the chemical reaction of iodine in the presence of water [3], the distillation method, in which moisture is determined by distillation with toluene, and the extraction method, which is carried out with absolute ethanol. 

In all cases, the reported R values was based on the added water, and were not corrected for any residual water that may have been in the dried-AOT or heptane solvent. Karl Fischer analysis of the AOT-heptane solutions before the addition of water resulted in an if value of 0.4. This amount was considered to be negligible. 

Raisanen [990] has described a device consisting of a cylindrical sample bottle holder, a dry carrier gas flow system, and a moisture transducer as a non-toxic replacement for Karl Fischer analysis of plastics. The sample of test material contained in a 20 mL septum bottle is heated to a preset temperature, usually just below the softening point of the resin. Evolved volatiles in the bottle headspace are passed through a cold trap filter to an analysis cell where the moisture content of the flowing gas is measured. High boilers are filtered out. A sophisticated algorithm, which makes use of the fact that as the sample approaches total dryness the rate of evolution of water is proportional to the water remaining in the sample, allows accurate determination of the... 

Stern, M. Reagent selection in the Karl Fischer analysis of pharmaceutical products. Am. Lab. 38(4), 2006. 

Water content This is usually performed by Karl Fischer analysis, although azeotropic distillation is sometimes used. If the total of the nonvolatiles at 110 C and the water content account for 100% of the sample, then it is unnecessary to look for an organic solvent. 

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