A monosegmented-flow Karl Fischer titrator

A monosegmented volumetric Karl Fischer titrator is described to mechanize the determination of water content in organic solvents. The system is based on the flow-batch characteristics of the monosegmented analysis concept and employs biamperometry to monitor the progress of the titration. The system shows accuracy and precision that are highly independent of the flow rate, does not require calibration, and is carried out in a closed system capable of minimizing contact of the sample and reagents with ambient moisture. Sample volumes in the range of 40-300 μL are employed, depending on the water concentration. An automatic dilution is provided to deal with concentrated samples. The consumption of Karl Fischer reagent depends on the water content of the sample but is not larger than 100 μL. The system was evaluated for determination of water in ethanol and methanol in the range 0.02-0.5% (w/w). The average relative precision estimated in that range (9-3%) is comparable to that obtained with a larger volume commercial system and no significant difference was observed between the results obtained for the two systems at the 95% confidence level. A complete titration can be performed in less than 5 min employing the proposed system.     

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Abstract

The determination of the water content plays an important role in the analysis of pharmaceutical products, because very often the content is calculated with reference to the dry substance. In three laboratories the determination of water in folic acid was examined in a collaborative study. Using three samples, loss on drying was compared with Karl Fischer titration. It was observed that the repeatability of loss on drying experiments was reasonable but the reproducibility was poor. Karl Fischer titration gave good repeatability and reproducibility. Compared with Karl Fischer titrations, loss on drying results were observed to be low.     

Determination of water by flow-injection analysis with the karl fischer reagent

A method for the determination of water in organic solvents by flow-injection analysis (f.i.a.) is described. The method, which is based on the reaction between water and the Karl Fischer reagent, is capable of 120 determinations per hour. The concentration range 0.01–5% (v/v) of water can be covered by using a single Karl Fischer reagent solution. The results obtained with a specially constructed potentiometric detector showed a relative standard deviation of less than 0.5% (v/v). This value was about 3 times less than that obtained with a spectrophotometric detector. The f.i.a. technique is shown to offer some unique possibilities in minimizing interferences associated with the standard Karl Fischer batch titration method.     

Water determination of precursor solutions with oxidant cations by the Karl Fischer method: the YBCO-TFA case

Uncontrolled water content in non-aqueous precursor solutions can be a source of irreproducibility in thin film performance through changes in the gel network. Towards gaining control on the solution properties, water determination in metalorganic solutions of YBCO-TFA has been studied by the Karl Fischer titration in a volumetric-type unit. However, oxidizing cations usually present when preparing functional oxides by chemical solution routes severely interfere in the Karl Fischer analysis. In the case of YBCO-TFA, cupric ions in the initial solution oxidize the iodide produced in the Karl Fischer reaction back to iodine, which in turn feeds the titration reaction and consumes more water, causing a negative error in the analysis, which can be as large as 70%. However, such chemical interference of cupric salts can be modelled and quantified. A corrected Karl Fischer methodology is proposed for accurately measuring water content in YBCO-TFA solutions, which could be potentially extended to other precursor solutions containing oxidant cations.     

Determination of trace water in gas samples by an improved Karl Fischer coulometer.

The determination of trace water in gas samples, such as isobutene, chloromethane (polymeric staple gases) and SF6 by a conventional Karl Fischer coulometer is very difficult, because of the adsorption of trace water on the surface of sample pipe, the gasification of the liquefied samples, and the migration of moisture into the measuring cell from the surroundings. To solve these problems, we improved a device for coulometric determination of water by Karl Fischer method. The improved coulometer was used to determine the trace water in isobutene, chloromethane and SF6; RSD was less than 5%, and recoveries ranged from 94.1 to 109.1%, which is adequate for the analysis of industry.     

Determination of moisture content of single-wall carbon nanotubes

Several techniques were evaluated for the establishment of reliable water/moisture content of single-wall carbon nanotubes. Karl Fischer titration (KF) provides a direct measure of the water content and was used for benchmarking against results obtained by conventional oven drying, desiccation over anhydrous magnesium perchlorate as well as by thermogravimetry and prompt gamma-ray activation analysis. Agreement amongst results was satisfactory with the exception of thermogravimetry, although care must be taken with oven drying as it is possible to register mass gain after an initial moisture loss if prolonged drying time or elevated temperatures (120 °C) are used. Thermogravimetric data were precise but a bias was evident that could be accounted for by considering the non-selective loss of mass as volatile carbonaceous components. Simple drying over anhydrous magnesium perchlorate for a minimum period of 8-10 days is recommended if KF is not available for this measurement.     

Determination of the contents of water and moisture in milk powder

According to official methods the moisture content of milk powders is determined by drying techniques and the loss of mass defined as water content. The mass loss, detecting the volatiles evaporated under the applied conditions, is strongly dependent on the drying parameters. An ideal method should be able to determine “free water” without including “bound water” in the result. Two collaborative studies showed that drying methods are not capable of distinguishing between different binding forms of water and only the total water content, measured with Karl Fischer titration, provides results which can be attributed to a defined physical property. Results from two European collaborative studies are employed to evaluate three different drying techniques and Karl Fischer titration. Adsorption isotherms of skimmed milk powder at different temperatures were used to calculate the isosteric heat of sorption. Received: 3 April 2000 / Revised: 17 May 2000 / Accepted: 24 May 2000     

Comparison between amperometric and true potentiometric end-point detection in the determination of water by the Karl Fischer method

A rapid and sensitive method using true potentiometric end-point detection has been developed and compared with the conventional amperometric method for Karl Fischer determination of water. The effect of the sulphur dioxide concentration on the shape of the titration curve is shown. By using kinetic data it was possible to calculate the course of titrations and make comparisons with those found experimentally. The results prove that the main reaction is the slow step, both in the amperometric and the potentiometric method. Results obtained in the standardization of the Karl Fischer reagent showed that the potentiometric method, including titration to a preselected potential, gave a standard deviation of 0.001(1) mg of water per ml, the amperometric method using extrapolation 0.002(4) mg of water per ml and the amperometric titration to a pre-selected diffusion current 0.004(7) mg of water per ml. Theories and results dealing with dilution effects are presented. The time of analysis was 1-1.5 min for the potentiometric and 4-5 min for the amperometric method using extrapolation.     

Method for avoiding the interference of formamide with the Karl Fischer titration

 The Karl Fischer titration is based on a specific chemical reaction. Several measures exist to make all the water of insoluble samples accessible for the chemical reactants. The most efficient are the titration at elevated temperatures, the use of a homogenizer in the titration vessel and the modification of the polarity of the working medium (essentially methanol) by the addition of appropriate solvents like chloroform or formamide. It is known however that formamide interferes with the Karl Fischer reaction and so causes more or less false results. This effect increases with higher temperatures. A method is therefore presented to avoid this interference, even when working at the boiling point of the working medium. It takes advantage of the fact that the side reaction has a practically constant velocity, at least as long as usual titrations last. Thus, a constant additional consumption of Karl Fischer reagent is observed. This can be accounted for by measuring this effect before the start of the determination and by deducting the additional reagent consumption, which is proportional to the duration of the titration, from the totally added volume. With certain modern titrators this can even be carried out automatically. They can continuously measure the so-called drift, the titration rate necessary to keep the titration cell dry, and have the capability to use this drift as stop criterion for the titration. This means that the analysis is terminated when the drift existing before the titration is reached again. The additional consumption of reagent, to be deducted from the total volume, can (automatically) be calculated from the drift rate and the titration time. The proposed procedure allows the use of formamide as additional solvent, even at high temperatures, in order to shorten determination times considerably. It avoids false results due to the interference, which has so far prevented its use when exact results were desired and when the duration of the analysis was long. Received: 30 May 1996 / Revised: 26 July 1996/Accepted: 30 July 1996     

Urea as the basic component in pyridine-free Karl Fischer reagent

A solution of urea, sulphur dioxide and sodium salicylate in methanol is proposed as the solvent in the Karl Fischer titration, with a separate iodine solution as titrant. Comparison of the performance of this solvent with that of some commercial reagents shows that it is has distinct advantages for use with amine samples.     

Determination of water (moisture) and dry matter in animal feed, grain, and forage (plant tissue) by Karl Fischer titration: collaborative study

A Karl Fischer method for determining water (dry matter) in animal feed and forages was collaboratively studied. Water was extracted from animal feed or forage material into methanol-formamide (1 + 1) directly in the Karl Fischer titration vessel by high-speed homogenization. The water was titrated at 50 degrees C with one-component Karl Fischer reagent based on imidazole. Ten blind samples were sent to 9 collaborators in the United States, Canada, and Germany. The within-laboratory relative standard deviation (repeatability) ranged from 1.14 to 6.99% for water or from 0.09 to 0.56% for dry matter. Among-laboratory (including within-) relative standard deviation (reproducibility) ranged from 5.35 to 10.73%, or from 0.44 to 0.77% for dry matter. The authors recommend that the method be adopted as Official First Action by AOAC INTERNATIONAL. A comparable alternative extraction procedure using boiling methanol is also recommended for Official First Action.     

卡尔菲休滴定仪测定液体石油产品中水含量

对运用卡尔菲休滴定仪库仑法测定液体石油产品中微量水的简单原理、分析方法的建立与分析流程进行了论述.实验结果表明,该方法测定结果的相对标准偏差为0.66%～1.30%(n=8),用该方法测定3种标准物质,其相对误差不大于2%.该方法分析快速、简便,适用于含有醇类、无机含氧弱酸特殊样品的测定.     

Impact of Sample Preparation on Residual Moisture Analyses for a Lyophilized Protein Formulation

This study compares residual moisture data obtained by thermogravimetric (TG) and Karl Fischer (KF) analyses of freeze-dried recombinant Desmodus rotundus salivary plasminogen activator (DSPA) and the protein free placebo. Significant changes in water content were observed depending on the sample type as well as the relative humidity of the exposure environment prior to analysis. The TG and KF analyses gave identical results only when the samples were handled identically. The method of choice for the determination of the true total moisture content of these samples is the KF analysis since it can be performed without any opportunity for water exchange with the environment.     

Interlaboratory assessment of measurement precision and bias in the coulometric Karl Fischer determination of water

The precision and bias of the coulometric Karl Fischer ASTM method D1533-00 have been assessed in a collaborative ASTM round robin program for a group of 34 laboratories. The test materials used in this study included water saturated 1-octanol (WSO), water saturated 1-butanol (WSB), and a series of new and used transformer oil samples. Fundamental systematic biases have been demonstrated in the accuracy of the measurement of water in the WSO, WSB, and transformer oil samples. The systematic bias in the measurement of the WSO and WSB standards indicates that for some laboratories either the instruments were not accurate or the quantity of the standard was not measured accurately. A second type of systematic bias consisted of measurement errors associated with the selection of the Karl Fischer solvent that was used with each instrument, and this was superimposed upon the error in the measurement of the water in the standards. Using the statistical calculation method ASTM D 6300 the repeatability and reproducibility for water in transformer oil were found to be 7 mg/kg and 14 mg/kg respectively. The method detection limit of water was 8 mg/kg oil. The method bias was estimated based on the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 2890, WSO, since no suitable reference material for water in transformer oil was available for this study.     

Validation of a gas chromatography/thermal conductivity detection method for the determination of the water content of oxygenated solvents

A gas chromatographic (GC) method for the determination of the water content of acetone solutions containing methyl isobutyl ketone (MIBK) and other by-products of MIBK synthesis was developed and validated. Linearity is demonstrated (R2=0.9999) over a broad range of water concentrations in acetone ranging from 0.04 to 15.2% (w/w). The quantitation limit (QL) of this technique was found to be 0.346% (w/w) and the detection limit (DL) was estimated to be 13ppm. Validation of this analytical method's accuracy against a coulometric Karl Fischer titration (KFT) method showed excellent agreement between these two techniques. The GC/TCD method is accurate to within a relative error of 3.49% with respect to the KFT method for water concentration above the QL. However, the analysis of six samples below the QL showed an average relative error of 10.96%. Consequently, the KFT method is recommended for the moisture analysis of samples for water concentrations below 0.35% (w/w). Excellent precision is realized for water concentration above the QL (RSD<0.8%). Good precision (RSD=1.1%) was obtained for the sample with the lowest water concentration investigated (0.04%, w/w). Repeatability, robustness and excellent specificity of this technique are demonstrated.     

Determination of water with a modified Karl Fischer reagent Stability and the mechanism of reaction with water

It is shown that the water equivalent of the modified Karl Fischer reagent (standard Karl Fischer reagent in which dimethylformamide is substituted for methanol), depending on pKa and the concentration of the solvent used for preliminary titration, is not dependent on the water concentration being determined. Also discussed are different aspects of the stability of the Karl Fischer reagent and its modifications. On the basis of the literature data and the findings of this work, a mechanism of interaction between water and the modified Karl Fischer reagent is proposed: in the first stage of the reaction pyridine sulphodioxide is solvated with solvents containing active hydrogen (alcohols, organic acids and water). The lower the value of pK_a of the solvent, the greater the contribution of water to the pyridine sulphodioxide solvation reaction. The results of this work suggest that, especially in particular cases, the water equivalent of the Karl Fischer reagent and its modifications should be determined under the same conditions as the determination of water in the sample.     

Determination of the water content of amphiphilic liquid crystals by coulometric Karl Fischer titration

An apparatus is described, which allows the precise determination of the water content of amphiphilic liquid crystals by means of coulometric Karl Fischer titration. The scope and limitations of this method are described.     

Assessment and assurance of quality in water measurement by coulometric Karl Fischer titration of petroleum products

The precise and accurate determination of water in petroleum products—gasoline, diesel oil and aromatic hydrocarbons—is of significant importance for their normal functional and operational characteristics for economics as well as in meeting international requirements. The standard method ISO 12937 for the measurement of water by the coulometric Karl Fischer titration method was subject to within-laboratory assessment. Thereby it was established that the analytical procedure could not always be relied upon, especially when low levels of water were determined. The aim of this work is to assess each stage of the test procedure depending on the particular problems defined by the samples, using high-reactive Karl Fischer reagents and coulometric cells with and without a diaphragm, and to indicate the major factors causing the uncertainty. A reduced combined uncertainty was achieved by modifying the sample preparation step, the administration of the moisture in the coulometric cell, and sample injection manipulation. Experiments showed that the cell without the diaphragm ensures lower and uniform uncertainty of the measurements in the range of 0.01 to 10 mg H₂O in comparison to the cell with a diaphragm and therefore is more appropriate for the determination of low water levels in the petroleum products. A procedure that utilized a mixture of the reagent and toluene (10:6) was able to resolve the problem of two phases of formation and reduced conductivity of the reagent in direct titration of diesel oils. The results suggest that the modified procedure ensures relative expanded uncertainty equal to or less than 2.0% (n=5, confidence interval close to 95%) and 99.4% recovery for petroleum products investigated in repeatability conditions.     

Mechanism and reaction rate of the karl fischer titration reaction: Part V. Analytical Implications

The Karl Fischer titration procedure for the determination of water has been studied. In view of the results of previous investigations, a methanolic sodium acetate—sulfur dioxide solution is recommended as solvent and an iodine solution in methanol as titrant. The advantages of this procedure over a conventional Karl Fischer titration are: a much more rapidly reacting reagent, the possibility of a visual end-point detection, a titrant of constant titre over a long period of time, and the absence of the disagreeable odour of pyridine.     

Determination of trace moisture in hydrogen chloride gas by Karl Fischer titration

Moisture of several ppm in hydrogen chloride gas has been accurately determined by a new method using the Karl Fischer reagent, which hitherto had a limitation in accuracy because of a partial reaction with hydrogen chloride when direct titration was employed.The moisture in the sample gas was collected in a cold trap kept at about ?80 °C while the hydrogen chloride gas passed through and the frozen moisture was dissolved by pyridine-methanol (1:1) solvent. a KF Reagent of factoe: 0.35 mg H₂O/ml.Titration by the Karl Fischer reagent having the equivalency factor of, e.g., 0.5 mg H₂O/ml was carried out and the concentration of the moisture was calculated from the sample volume used.