Applikationer

This article demonstrates the utility of portable Raman spectroscopy as a versatile tool for process analytical technology (PAT) for raw material identification, in-situ monitoring of reactions in developing active pharmaceutical ingredients (APIs), and for real-time process monitoring. Raw material identification is done for verification of starting materials as required by PIC/S and cGMP, and can be readily done with handheld Raman. Portable Raman systems allow users to make measurements to bring process understanding and also provide proof of concept for the Raman measurements to be implemented in pilot plants or large-scale production sites. For known reactions which are repetitively performed or for continuous online process monitoring of reactions, Raman provides a convenient solution for process understanding and the basis for process control.

Quantitation of the functionalization of a water-soluble polymer was achieved using a portable Raman spectrometer. The Raman spectrum provides strong, unique bands for both the initial and fully reacted polymer. This enables development of a simple, robust quantitative analysis of the percent polymer functionalization. This method is now routinely used in a manufacturing plant's quality control laboratory.

Although the process of building, validating and using a method is well-defined through software, the robustness of the method is dependent on proper practice of sampling, validation, and method maintenance. In this document, we will detail the recommended practices for using the multivariate method with NanoRam-1064. These practices are recommended for end users who are in the pharmaceutical environment, and can expand to other industries as well. This document aims to serve as a general reference for NanoRam-1064 users who would like to build an SOP for method development, validation and implementation.

Raman spectroscopy’s use for process analytics in the pharmaceutical and chemical industries continues to grow due to its nondestructive measurements, fast analysis times, and ability to do both qualitative and quantitative analysis. Spectral preprocessing algorithms are routinely applied to quantitative spectroscopic data in order to enhance spectral features while minimizing variability unrelated to the analyte in question. In this technical note we discuss the main preprocessing options pertinent to Raman spectroscopy with real applications examples, and to review the algorithms available in B&W Tek and Metrohm software so that the reader becomes comfortable applying them to build Raman quantitative models.

Hydroxyl is an important functional group and knowledge of its content is required in many intermediate and end-use products such as polyols, resins, lacquer raw materials and fats (petroleum industry). The test method to be described determines primary and secondary hydroxyl groups. The hydroxyl number is defined as the mg of KOH equivalent to the hydroxyl content of 1 g of sample.The most frequently described method for determining the hydroxyl number is the conversion with acetic anhydride in pyridine with subsequent titration of the acetic acid released: H3C-CO-O-CO-CH3 + R-OH -> R-O-CO-CH3 + CH3COOH. However, this method suffers from the following drawbacks: - The sample must be boiled under reflux for 1 h (long reaction time and laborious, expensive sample handling) - The method cannot be automated - Small hydroxyl numbers cannot be determined exactly - Pyridine has to be used, which is both toxic and foul-smellingBoth standards, ASTM E1899-08 and DIN 53240-2, offer alternative methods that do not require manual sample preparation and therefore can be fully automated: The method suggested in ASTM E1899-08 is based on the reaction of the hydroxyl groups attached to primary and secondary carbon atoms with excess toluene-4-sulfonyl-isocyanate (TSI) to form an acidic carbamate. The latter can then be titrated in a non-aqueous medium with the strong base tetrabutyl- ammonium hydroxide (TBAOH). The method suggested in DIN 53240-2 is based on the catalyzed acetylation of the hydroxyl group. After hydrolysis of the intermediate, the remaining acetic acid is titrated in a non-aqueous medium with alcoholic KOH solution. The present work demonstrates and discusses an easy way to determine the hydroxyl number according to ASTM E1899-08 or DIN 53240-2 with a fully automated titrimetric system for a great variety of industrial oil samples.

The presence of excessive water in plastics adversely affects the performance of polymeric goods which is why water determination is of crucial importance. This article describes the accurate and straightforward determination of the water content using the Karl Fischer Oven Method in ten different plastic types that are not amenable to direct Karl Fischer titration. The experiments revealed that besides the determination of the oven temperature, sample preparation is one of the most important steps of the analysis, especially in case of hygroscopic plastic samples.

The Combustion IC system presented allows the automated determination of organic halogen and sulfur compounds in all flammable samples. Both combustion digestion, which is automatically controlled with a flame sensor, and the professional Liquid Handling guarantee highest precision and trueness. This poster describes the determination of the halogen and sulfur content in a certified polymer standard, a coal reference material as well as in latex and vinyl gloves.

Carbonyl compounds (CC) occur in many products, such as bio-oils and fuels, cyclic and acyclic solvents, flavors and mineral oils. Carbonyl compounds can be responsible for the instability of these products during storage or processing. Especially pyrolysis bio-oils are known to cause issues during storage, handling and upgrading. This bulletin describes an aqueous and a non-aqueous analytical titration method for the determination of carbonyl compounds by potentiometric titration.

Indication of the titration endpoint of the weakly alkaline or weakly acidic terminal groups in non-aqueous solution is frequently not easy. An improvement is possible by using a suitable titrant (TBAH = tetrabutylammonium hydroxide for terminal carboxyl groups; perchloric acid for terminal amino groups).An improvement in the evaluation can also be achieved by choosing benzyl alcohol as the solvent.The choice of electrode combination and the measuring setup is also important. Differential potentiometry using the three-electrode technique results in a great improvement in titrations in poorly conducting solutions. Noisy signals are eliminated.

This Application Bulletin gives an overview of the volumetric water content determination according to Karl Fischer. Amongst others, it describes the handling of electrodes, samples, and water standards. The described procedures and parameters comply with the ASTM E203.

This Application Bulletin describes a simple polarographic method to determine monomeric styrene in polymers. The limit of determination lies at 5 mg/L. Before the determination, styrene is converted to the electrochemically active pseudonitrosite using sodium nitrite.

This Application Bulletin gives an overview of the coulometric water content determination according to Karl Fischer.Amongst others, it describes the handling of electrodes, samples, and water standards. The described procedures and parameters comply with the ASTM E1064.

Maleic and fumaric acid can be reduced electrochemically to succinic acid. In acidic solutions a differentiation of the two acids is not possible since both are reduced at the same potential. On the other hand, separation at pH 7.8...8.0 is easily possible since fumaric acid is now more difficult to reduce at the lower proton concentration (as a result of cis-trans isomerism) than maleic acid.

4-Carboxybenzaldehyde, in the following referred to as 4-CBA, can be reduced directly at the dropping mercury electrode (DME) in an ammoniacal solution. After a very simple sample preparation it is now possible to determine the concentration of 4-CBA in terephthalic acid quickly and precisely by polarography down to the lower ppm range.

Polyurethanes are one of the most commonly used types of plastic. They are produced by the reaction of raw polyols with isocyanates. Depending on the starting material a wide variety of plastics can be obtained. The determination of the acid value, hydroxyl value, and isocyanate content plays an important part in the analysis of raw materials for plastics.The acid number of polyol raw material is usually used in quality control to ensure batch-to-batch uniformity. Additionally it is used as correction factor for calculating the true hydroxyl number. In this Application Bulletin the determination of the acid number according to ASTM D4662 and ASTM D7253 is described.One raw material for polyurethanes are polyols. Polyols contain multiple hydroxyl groups. Therefore, hydroxyl number of a raw material directly correlates to the amount of polyols present and it is thus an important quality control parameter. In this Application Bulletin the determination of the hydroxyl number according to ASTM E1899 and DIN 53240-3 is described.As polyols react stoichiometrically with isocyanates, the knowledge of the isocyanate content is an important quality parameter for the production of polyurethanes. In this document the determination according to EN ISO 14896 method A, ASTM D5155 method A and ASTM D2572 is described.

This Application Bulletin describes the determination of the thermostability of PVC in accordance with ISO 182 Part 3 using the dehydrochlorination method with the 895 Professional PVC Thermomat. The instrument permits fully automatic determination of the stability time. The test is suitable for monitoring the manufacture and processing of PVC products manufactured in the injection molding process, for their final clearance, characterization and for the comparison of PVC products and for testing the effectiveness of heat stabilizers.

Generally speaking, the gas extraction or oven method can be used for all samples which release their water when they are heated up. The oven method is indispensable in cases in which the direct volumetric or coulometric Karl Fischer titration is not possible, either because the sample contains disruptive components or because the consistency of the sample makes it very difficult or even impossible to transfer it into the titration vessel.The present Application Bulletin describes automatic water content determination with the aid of the oven technique and coulometric KF titration, using samples from the food, plastic, pharmaceutical and petrochemical industry.

The presented titration system can be used for the fully automated determination of the hydroxyl number (HN) according to ASTM E1899 and EN ISO 4629-2. The method allows, the determination of polyols and oxooils without boiling under reflux or other sample preparation and is therefore a big benefit for laboratories that have to cope with a high sample throughput.The standards EN 15168 and DIN 53240-3 relay on the same analysis method as in ASTM E1899.

This bulletin describes a procedure to determine the bromine index (BI) using coulometric titration. The bromine index is the fraction of reactive unsaturated compounds (mostly C=C double bonds) in hydrocarbons encountered in the petrochemical industry. The double bonds are split with the attachment addition of bromine.

The present Application Bulletin elucidates several applications for the polymer industry that can be carried out with the aid of NIR instruments. This Bulletin contains analyses of a wide range of parameters in a very large array of samples. The hydroxyl number is one of the best-known of the parameters that can be determined rapidly using near-infrared spectroscopy. The determination of the hydroxyl number in different areas and in different polyol types is also a part of this Bulletin. Each application describes the sample and the instrument that was originally used for the analysis, as well as the recommended instruments and the results.

This method is applicable to all samples containing glycerin in the absence of other triols or other compounds that react with periodate to produce acidic products. Glycerin may be determined in the presence of glycols. A periodate solution reacts slowly with diols and triols in acidic aqueous media at room temperature. A quantitative amount of formic acid is generated from the reaction with glycerin (a triol). The reaction with diols produces neutral aldehydes. The amount of formic acid generated by this reaction is determined by titration against sodium hydroxide.

Determination of sodium, ammonium, and potassium in polyethers using cation chromatography with direct conductivity detection.

Determination of sodium and potassium in a polyol solution using cation chromatography with direct conductivity detection.

Determination of traces of methylamine, dimethylamine, and trimethylamine in methylpyrrolidone using cation chromatography with direct conductivity detection.

Polyols are important raw materials in polyurethane production. Contamination in the raw materials have a great influence on reactions and impair the quality of the end product. Alkali metals are particularly strong catalysts for linear or branched reactions. A rapid and precise method for their simultaneous determination is ion chromatography following Inline Matrix Elimination.

1,3,5-trioxane is a heterocyclic compound formed by trimerization of formaldehyde. Trioxane is used for the production of polyformaldehyde plastics such as poly(oxymethylene) (POM) and solid fuels. Aqueous 1,3,5-trioxane solutions frequently contain trace triethylamine that requires quantification. This is performed on the Metrosep C 3 - 250/4.0 column with subsequent direct conductivity detection.

The determination of halogens and sulfur in waste products is important. The inline combination of the Mitsubishi Combustion Module with the Metrohm IC is a suitable method for this type of samples. The recovery rates are analyzed with a certified reference material, e.g., a low-density polyethylene (LDPE).Keyword: pyrohydrolysis

Latex gloves are used in clean room environments in order to prevent contaminations. The use of gloves that release corrosive halogenides or sulfate is forbidden in nuclear power plants. The total content of halogen and sulfur is determined by means of Combustion Ion Chromatography. An eluate test is carried out to check the elutable percentage of halogens and sulfate from gloves. Sample preparation is comprised of preconcentration and matrix elimination (MiPCT-ME), as described in AN-S-304.Keyword: pyrohydrolysis

Combustion Ion Chromatography combines pro-hydrolytic sample combustion and the absorption of emerging combustion gases in an oxidizing, aqueous solution that is then channeled to an ion chromatograph for the analysis of halogenides and sulfur (as sulfate). The combustion and analysis of the certified reference materials (ZRM) makes clear the reliability of Metrohm Combustion Ion Chromatography.Keyword: pyrohydrolysis

Polyisobutene (PIB) is an important raw material for a large range of products. Quality control requires the determination of the fluorine content. This task is easily done by Metrohm Combustion IC applying flame sensor technology and Inline Matrix Elimination.Keyword: pyrohydrolysis

The Restriction of Hazardous Substances Directive (RoHS) requires to reduce the halogen content in several organic materials used in electrical and electronic equipment. In this context, there is a huge interest for using halogen-free polymers. To check for halogens in polymers according to standard IEC 60754, Metrohm Combustion IC applying flame sensor technology and Inline Matrix Elimination is an indispensable method. The examined polymeric material contains halogens at a level of up to 1%.

Halobutyl rubber is frequently used in the production of pharmaceutical stoppers. It is ideal for this application due to its low permeability to gases and its chemical resistance. Chlorinated and brominated butyl rubber stoppers are analyzed for their halogen and sulfur content. Halogen and sulfur compounds are released by pyrohydrolysis and analyzed by subsequent ion chromatography (IC).

Polystyrol is brominated to increase flame retardation. The brominated polystyrene finally consists of 25 to 35% of bromine. The determination of bromine by combustion ion chromatography (CIC) requires a specially optimized absorption solution to trap all bromide. This work shows the optimization of the absorption solution for high-bromine samples.

Polymer materials that are used for building and decoration purposes need to be flame resistant. To reach the required level of resistance flame-retardants are added to the plain polymer. Flame-retardants are often haloorganic compounds. The use of such components and the respective concentration of introduced halogens can be determined by Combustion IC. The recovery over the full system is tested with acertified reference material (CRM).

Cellulose ester foils are produced using chlorinated solvents. The residual amount of the solvent used in production evaporates within a few days in ambient conditions. The residual solvent is determined by combustion IC, through the conversion of organically bound chlorine to chloride by pyrohydrolysis. The final product needs to be free of all chlorinated solvents. Therefore, critical contents of such compounds can be detected in quality control analysis. Application of MiPT in this study has enabled an automated and precise calibration out of a single standard.

AOF (adsorbable organic fluorine) is used to screen for per- and polyfluorinated alkyl substances in aqueous matrices via pyrohydrolytic combustion and ion chromatography.

Combustion ion chromatography (CIC) measures AOX (adsorbable organically bound halogens, i.e., AOCl, AOBr, AOI) and AOF as well as CIC AOX(Cl) according to DIN 38409-59 and ISO/DIS 18127.

Organic halides must be monitored in the environment. Combustion ion chromatography (CIC) is used for accurate halogen analysis in solids following EN 17813:2023.

A reference electrode has a stable and well-defined electrochemical potential (at constant temperature), against which the applied or measured potentials in an electrochemical cell are referred. A good reference electrode is therefore stable and non-polarizable. In other words, the potential of such an electrode will remain stable in the used environment and also upon the passage of a small current. This application note lists the most used reference electrodes, together with their range of use.

The TSC SW Closed and TSC Battery cells are compact systems designed for measurements on air or moisture-sensitive materials, such as those used in batteries. In this document, two testing procedures are explained. The first procedure is withpotentiostatic cyclic voltammetry (CV), while the second is via electrochemical impedance spectroscopy (EIS).

In the application note AN-EIS-004 on equivalent circuit models, an overview of the different circuit elements that are used to build an equivalent circuit model was given. After identifying a suitable model for the system under investigation, the next step in the data analysis is estimation of the model parameters. This is done by the non-linear regression of the model to the data. Most impedance systems come with a data-fitting program. In this application note, the way NOVA is uses to fit the data is shown.

In this application note, the advantage of recording the raw time domain data for each individual frequency during an electrochemical impedance measurement is described.

Acrylic dispersion paints are made of pigment suspended in acrylic polymer emulsions, which also include other organic material such as plasticizers, defoamers, or stabilizers. Acrylic dispersion paints are water-soluble but become resistant to water when dry. Due to the fact that once dry, acrylic dispersion paints can no longer be used, they should be stored air-tight at room temperature. For research purposes, it is of interest to assess the dissolved oxygen (DO) concentration in such samples as it is assumed that the DO amount can be related to the storage life. This Application Note describes a fast and accurate determination of dissolved oxygen by using an optical sensor.

The water content of plastic chips is determined according to Karl Fischer. Because of the low water content of the sample, the oven method (200 °C) and coulometric titration have to be used.

The water content of organic peroxides is determined according to Karl Fischer using two-component reagents. To prevent any unwanted side reactions, the determinations are carried out at -20 °C.

The presence of water in expandable polystyrene (EPS) can have a negative impact on the thermal insulation properties, as it increases thermal conductivity. If EPS is exposed to a high moisture environment, additional water may be absorbed, which can further affect thermal insulation.Direct analysis of the moisture content by Karl Fischer titration requires the water to be extracted from the EPS, which involves several time-consuming steps. Therefore, determination of the water content with an oven system is preferred. As EPS expands when heated, the use of sample boats, as required by ASTM D6869, is not possible, as the EPS will contaminate the oven system. This Application Note describes the determination of water content in EPS using an oven system with closed sample vials. A determination takes about 7 to 14 min depending on the water content of the sample and the sample size.

In this application note, Karl Fischer titration is used to determine the water content of urea.

The water content of 2-methyl-1,3-butadiene and 2,5-norbornadiene is determined according to Karl Fischer using a special solvent mixture to prevent unwanted side reactions.

The water content of piperidine and piperazine is determined according to Karl Fischer using a buffered solvent mixture.

The water content of melamine is determined according to Karl Fischer in a buffered solvent mixture at 50 °C.