Sample Preparation Using Dissolution Method

Polycarbonate Dimethyl acetamide Metal naphthanates and others 

Cellulose 50% cone. HCI + H2SO4 Metal naphthanates and others 

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When samples are prepared using dissolution methods, the true analytical blank consists of all reagents and steps used In the method. The only analyte present In this second type of blank Is caused by contamination from any reagent or contact with laboratory environment and apparatus. The level of analyte In this analytical blank and Its variability are key quantities to be evaluated In accurate trace analysis (16). The content of the analytical blank Is more method dependent than that of the reagent blank. 

The detection limits for determination of the DA using C NMR and N NMR spectroscopy reported to be 10%. NMR and N NMR techniques are not appropriate techniques for chitin/ chitosan having low DA values. These two NMR techniques resulted in underestimates values for low DA values (Domard 1987, Raymond et al. 1993, Heux et al. 2000). The margin of error for the DA obtained by H NMR spectroscopy reported to be around 5% (Hirai et al. 1991, Varum et al. 1991a, Rinaudo et al. 1992, Kasaai et al. 1999, Heux et al. 2000). C NMR and N NMR can be used for entire range of the DA. Solid-state NMR O C and N) spectroscopy has been used to determine the DA of insoluble samples sueh as cross-linked and block copolymers. CP/MAS, C NMR, and CP/MAS N NMR do not need sample preparation for dissolution and are appropriate methods for insolnble chitin/chitosan samples even the samples are associated with impurities and humidity (Ottpy et al. 1996). 

QA requires the efficient analysis of many samples to support routine production release and stability programs. Methods are typically established in the analytical development group. Efficiency and convenience issues, including the speed of media preparation and the relative convenience of data handling and documentation, are important here. While compliance is important in all aspects of the pharmaceutical industry, QA functions must approach compliance perfection. Depending upon the facility, the automated apparatus may be tailored to specific methods with fixed configurations. Dissolution methods may be routine enough that a custom system, optimized for productivity, may be justified. Compliance of USP and use of industry standard apparatus is important to maintain compatibility with other company laboratories or in the case contract laboratory services are required. 

Usually, samples are presented for analysis as liquids. Thus, solid samples must be dissolved. Analytical or ultra-high-purity grade reagents must be used for dissolution to prevent contamination at trace levels. Certain volatile metals (e.g. cadmium, lead and zinc) may be lost when dry ashing, and volatile chlorides (e.g. arsenic and chromium) lost upon wet digestion. It is particularly easy to lose mercury during sample preparation. Appropriate steps must be taken in the choice of method of dissolution, acids and conditions (e.g. whether to use reflux conditions) to prevent such losses. 

The validation requirements are discussed as they apply to both the sample preparation and sample analysis aspects of a dissolution method. The focus of the discussion in this chapter is on the validation considerations that are unique to a dissolution method. Validation is the assessment of the performance of a defined test method. The result of any successful validation exercise is a comprehensive set of data that will support the suitability of the test method for its intended use. To this end, execution of a validation exercise without a clearly defined plan can lead to many difficulties, including an incomplete or flawed set of validation data. Planning for the validation exercise must include the following determination of what performance characteristics to assess (i.e., strategy), how to assess each characteristic (i.e., experimental), and what minimum standard of performance is expected (i.e., criteria). The preparation of a validation protocol is highly recommended to clearly define the experiments and associated criteria. Validation of a test method must include experiments to assess both the sample preparation (i.e., sample dissolution) and the sample analysis. ICH Q2A [1] provides guidance for the validation characteristics of the dissolution test and is summarized in Table 4.1. 

Different approaches may be used to validate the sample preparation component of the dissolution test. However, it is important to understand that the objective of validation is to demonstrate that the procedure is suitable for its intended purpose. For example, one of the strategies will demonstrate the validity of different aspects of sample preparation during method development (prior to the formal method validation exercise). As a result, the final validation experiments will confirm the work done during method development. The strategy that will be followed for the method development and validation process will depend on the culture, expertise, and strategy of the analytical laboratory. 

Precision Intermediate Precision. Sets of six dissolution samples that are prepared using different instruments and by different analysts are used to determine intermediate precision. However, this procedure will not be able to differentiate method variation versus tablet-to-tablet variation. It will predict the worst-case precision that includes tablet-to-tablet, sampling, and analysis variations. 

Methods involve extractions of analytes into organic solvents, as well as treatments with acidic or basic reagents. Solid-phase extraction can be used for removal and pre-concentrations of analytes in aqueous solutions. Applications of low-power focused microwave technology have been investigated as a means of dissolution, and good results have been reported for extractions of organometal-lic compounds of tin and mercury (Schmitt et al., 1996 Szpunar et al., 1996). Analyses of CRMs were used for verification. The time necessary for quantitative isolations of the analytes was greatly reduced, e.g. 24 h to 5 min. In addition, there were reductions in solvent volumes, and improvement in analyte recoveries. Some of the analytical procedures for speciation of particular elements such as mercury, described later in this chapter, include microwave-assisted sample preparation. 

A common result of the sample preparation is the dissolution of the entire sample, producing a clear solution. The digestion method must be selected to suit the type of sample, the metals being determined, and finally, the analytical method. Of the methods listed above, most require a liquid sample, except for x-ray fluorescence, which often is used on solid samples. Wet digestion in acid solution, dry ashing, and extraction of the analytes from... 

The second example in Table 10 demonstrates the advantages of this silica approach [308]. Using a mobile phase of methanol-water (75 25) buffered with ammonium phosphate at pH = 7.8, various syrups and tablets were analyzed for antihistamines, antitussives, and decongestants. A comparison between reversed-phase and silica methods of similar cough syrups clearly demonstrates that peak responses obtained by the aqueous silica method are more symmetric than the reversed-phase methods (compare Figure 5.8 with Figure 5.9). In addition, the sample preparation procedures in the silica method are relatively simple, requiring dilution for syrup formulations and dissolution for tablets. 

A novel approach was described for the speciation analysis of Hg, namely methyl-Hg and Hg(II), in Fsh tissue using GC-MIP-AES [36]. Focused MW-assisted digestion was applied for sample preparation (tissues were dissolved with TMAH, 25 percent aqueous solution), a technique which enables mild, quick, and complete dissolution of the sample. The method was validated by analysis of the BCR 464 freeze-dried tuna E>sh CRM. 

The method of sample preparation to be used for a given analysis is governed by the nature and concentration of the analyte, the nature (solid or liquid) and type of matrix, the available sample amount, and also by the instrumental technique employed. Freeze-dried samples will require some form of digestion or dissolution in order to be analyzed by a classic atomic technique (i.e., using nebuliza-tion). Liquids might be analyzed by direct nebulization, but this is not always possible due to matrix interferences. Milk pretreatment may be necessary under such circumstances. 

Basically, the literature provides two dissolution methods sample preparation with sample weights of 0.2—1 g and large dilutions, or smaller sample weights with less dilution (III.B). The relatively large dilution, in general after a fusion [51], for the determination of main and lesser components, as for example in silicate analysis [2], the determination of Al, Ca, Mg, Mn and Si in slags [4], Si [55], Pb and Mn [143], and also Cd, Ca, Cu, Pb, Mg and Si in ores or iron sinter [97, 147] and Cr, Mg in refractories [93] is presently used in routine analysis. 

The book begins with a discussion of the basic physico-chemical aspects of reactions utilised in qualitative inorganic analysis. A description of laboratory equipment follows, and operations which include semimicro and micro techniques, and simple electrochemical, spectroscopic and chromatographic methods. The reactions of the most important cations and anions are described, followed by a treatment of systematic qualitative analysis. Sample preparation, dissolution and fusion of insoluble materials are treated in detail. A separate chapter deals with the reactions of less common ions, with guidelines to their separation and identification in the course of systematic analysis. Finally, a simplified course of qualitative analysis is given this chapter will be particularly useful where the time allocated to qualitative analysis is limited. 

Demonstrating that the analytical method used is accurate is equivalent to showing that the stages of sample preparation (dissolution, extraction etc.), which can break the chain of traceability, do not cause systematic error. The results of the measurements are then traceable to the units in which the certified values are expressed. 

The first step in analysing plastics for metals content in polymers by ICP-AES technique is that they must be prepared in solutions that are suitable for nebulization. There are four general methods applicable for sample preparation for metal analysis by ICP-AES and they are solvent dissolution of some plastics dry ashing using a muffle furnace acid digestion using a microwave oven and oxygen bomb combustion. 

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