Validated methods of analysis

To confirm the rapid degradation of DMDC (dimethyl dicarbonate) (E242) in nonalcoholic drinks and to develop and validate methods of analysis for the detection and quantification of the use of the sterilant. 

Thus, as for the European Union, the requirements are based on accreditation, proficiency testing, the use of validated methods of analysis and, in addition, the formal requirement to use internal quality control procedures which comply with the Harmonised Guidelines. Although the EU and Codex Alimentarius Commission refer to different sets of accreditation standards, the ISO/IEC Guide 25 1990 and EN 45000 series of standards are similar in intent. It is only through these measures that international trade will be facilitated and the requirements to allow mutual recognition to be fulfilled will be achieved. 

Assays Validated methods of analysis (e.g., ELISA for MAb), QPCR for residual DNA, and potency assays for vaccines... 

The European Commission has mandated the European Committee for Standardization to establish a validated method of analysis for the determination of OMLs and SMLs. If a product complies with the compositional requirements of the directives, i.e., it is produced from authorized monomers and additives, then it may be tested for any desired application. If it meets the migration requirements, it is acceptable for use in cases covered by that test method. Typical food simulants used in the tests are hot water, acetic acid, ethyl alcohol and olive oil. The choice of an appropriate simulant depends on the type of food expected to come into contact with the packaging. 

In the following, a practical guide for a step-by-step procedure is presented to establish a validated method of analysis both for determination of a specific migrant in a food simulant and the residual concentration in a plastic. This procedure was first developed and then applied in a European project (Franz and Rijk 1997) and found to be very practical. It should be considered as a recommendation based on the great practical experience of the analysts involved. 

The scope of this chapter is limited to troubleshooting HPLC systems using predeveloped and validated methods of analysis. We will focus on some of the most commonly encountered problems and the possible solutions. 

There is an obvious order to these four facets of analytical methodology. Ideally, a protocol uses a previously validated procedure. Before developing and validating a procedure, a method of analysis must be selected. This requires, in turn, an initial screening of available techniques to determine those that have the potential for monitoring the analyte. We begin by considering a useful way to classify analytical techniques. 

The Environmental Protection Agency (EPA) authorizes control over hazardous and potentially hazardous substances and validates appropriate methods of analysis, many of which require GC/MS. 

Decision analytic models, or simulation models of clinical decision analysis, usually involve the creation of a treatment decision/outcome tree based on a synthesis of expert opinion, sometimes using validated methods of canvassing opinion such as recruiting a Delphi panel (Hatziandreu et al, 1994 Einarson et al, 1995). The decision tree... 

The use of reference samples for method calibration and development/validation occurred hand-in-hand with the development of all modern instrumental methods of analysis. In fact, the two developments are intimately linked with one another. As already noted, G-i and W-i (Fairbaim et al. 1951 Stevens i960) illustrate first instance of reference samples specifically developed for calibration purposes. Following that, the use of BCR-i as a reference sample throughout the lunar program (Science 1970) is a prime illustration of the quality assurance and method validation applications in large-scale inter-laboratory measurement programs. 

Established in 1894, AOAC International is an independent association of scientists and organizations in the public and private sectors devoted to promoting methods validation and quality measurements in the analytical sciences. AOAC has a mission to ensure the development, testing, validation, and publication of reliable chemical and biological methods of analysis for foods, drugs, feed-stuffs, fertilizers, pesticides, water, forensic materials and other substances affecting public health and safety and the environment. 

Several of the chapters in the current volume are comprehensive in nature, but others are more specialized. Volume 32 also contains a methodology review article on the validation of chromatographic methods of analysis. New to the series are annual reviews, and volume 32 contains a summary of the publications appearing during 2004 that dealt with polymorphism and solvatomorphism. It is anticipated that future volumes in the Profiles series will contain similar methodology reviews, as well as other types of review articles that summarize the current state in a particular field of pharmaceutics. As always, I welcome communications from anyone in the pharmaceutical community who might want to provide an opinion or a contribution. 

Horwitz points out the universal recognition of irreproducible differences in supposedly identical method results between laboratories. It has even been determined that when the same analyst is moved between laboratories that the variability of results obtained by that analyst increases. One government laboratory study concluded that variability in results could be minimized only if one was to conduct all analyses in a single laboratory. .. by the same analyst . So if we must always have interlaboratory variability how much allowance in results should be regarded as valid - or legally permissible as indicating identical results. What are the practical limits of acceptable variability between methods of analysis - especially for regulatory purposes. 

In analytical chemistry, we do not have a standard mole. Therefore, solutions made up to a well-defined concentration using very pure chemicals are used as a basis from which we can compare other solutions or an instrument scale. This process is calibration . For some analyses, the chemical used may be a Certified Reference Material which has a well documented specification, e.g. in terms of the concentration of a particular species and the uncertainty of the specified value. However, it is not sufficient just to calibrate the apparatus/equipment used, it is important that the complete method of analysis is validated from extraction of the analyte from the sample to the final measurement. 

If the validated test method requires 1 g of material but only 100 mg is available, you must find out if the method is sufficiently robust to stand this amount of scaling down. This has to be checked before the analysis starts, i.e. the method must be validated for analysis of 100 mg of material. Even if the method of analysis is found to be robust, scaling down is only a viable option if the smaller test portion size remains representative, within acceptable limits. This will depend on the homogeneity of the material. 

Sampling procedures are extremely important in the analysis of soils, sediments and sludges. It is essential to ensure that the composition of the portion of the sample being analysed is representative of the material being analysed. This fact is even more evident when it is conceded that the size of the portion of sample being analysed is in many modern methods of analysis extremely small. It is therefore essential to ensure before the analysis is commenced that correct statistically validated sampling procedures are used to ensure as far as is possible that the portion of the sample being analysed is representative of the bulk of material from which the sample was taken. 

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