Validation IUPAC

AOAC/FAO/IAEA/IUPAC Expert Consultation, Guidelines for Single Laboratory Validation of Analytical Methods for Trace-level Concentrations of Organic Chemicals, Workshop, 8-11 November 1999, Miskolc, Hungary (1999). Also available on the Word Wide Web http //www.iaea.oi trc/(see pesticides —> method validation). 

Depending on the type of relationships between the measured quantity and the measurand (analytical quantity) it can be distinguished (Danzer and Currie [1998]) between calibrations based on absolute measurements (one calibration is valid for all1 on the basis of the simple proportion y = b x, where the sensitivity factor b is a fundamental quantity see Sect. 2.4 Hula-nicki [1995] IUPAC Orange Book [1997, 2000]), definitive measurements (b is given either by a fundamental quantity complemented by an empirical factor or a well-known empirical (transferable) constant like molar absorption coefficient and Nernst factor), and experimental calibration. 

Apart from the fact that both the fundamental constants b and the conditions under which they are valid (e.g. under which a reaction proceeds quantitatively) sometime were determined and have to be updated from time to time (e.g., on the basis of IUPAC documents). 

Selectivity and specificity are important performance characteristics of analytical procedures, especially in connection with validation processes. Nevertheless, both terms are used mostly verbal and a quantification is avoided, as a rule (IUPAC see Vessman et al. [2001]). Moreover, the concepts of selectivity and specificity are used interchangeably and synonymously. Occasionally, specificity is regarded as an intensification of selectivity, viz. the ultimate of selectivity (den Boef and Hulanicki [1983] Persson and Vessman [1998, 2001] Prichard et al. [2001]). 

As stated by IUPAC [5], a validation method can be differentiated into categories of fully validated and single-laboratory method validation. A fully validated... 

By using the combination of specific method accreditation and generic accreditation it will be possible for laboratories to be accredited for all the analyses of which they are capable and competent to undertake. Method performance validation data demonstrating that the method was fit-for-purpose shall be demonstrated before the test result is released and method performance shall be monitored by on-going quality-control techniques where applicable. It will be necessary for laboratories to be able to demonstrate quality-control procedures to ensure compliance with the EN 45001 Standard,3 an example of which would be compliance with the ISO/AOAC/IUPAC Guidelines on Internal Quality Control in Analytical Chemistry Laboratories.12... 

There is concern in the food analytical community that although methods should ideally be validated by a collaborative trial, this is not always feasible for economic or practical reasons. As a result, IUPAC guidelines are being developed for single laboratory method validation to give information to analysts on the acceptable procedure in this area. These guidelines should be finalised by the end of 2001. 

On the international level, we distinguish IUPAC, ISO, and the AOAC International. All three bodies develop validation and standardization frameworks for analytical chemistry. AOAC International introduced the AOAC Peer Verified Methods Program [62]. Different harmonized guidelines and protocols are developed by the IUPAC, ISO, and AOAC International together [4,8,63-67], in addition to a number of ISO standards [68-71]. The FDA, USP, and ICH developed guidelines specific for pharmaceutical and biotechnological methods [55,72-74]. 

IUPAC, ISO, and AOAC International International Union of Pure and Applied Chemistry, International Organisation for Standardization, Association of Official Chemists Method validation, Standardization, internal quality control, proficiency testing, accreditation 4,8, 62-71... 

The literature gives a wide range of practical guidelines for the evaluation of method performance characteristics [58]. Besides the diversity of approaches, also the terminology and way of reporting results vary widely. Differences may occur depending on the purpose and the application field of the method, and validation studies may become more difficult as the complexity of the analysis increases [86]. In what follows, terms and formulas are taken from the accepted IUPAC nomenclature for the presentation of results of chemical analysis [66]. For each validation parameter, definitions, ways of expression, determination guidehnes, and acceptance criteria are reported in Table 5. 

Thompson, M., Ellison, S., and Wood, R. (2002), Harmonised guidelines for singlelaboratory validation of methods of analysis, IUPAC Technical Report, Pure Appl. Chem., 74,835-855. 

Limit of detection (LOD) sounds like a term that is easily defined and measured. It presumably is the smallest concentration of analyte that can be determined to be actually present, even if the quantification has large uncertainty. The problem is the need to balance false positives (concluding the analyte is present, when it is not) and false negatives (concluding the analyte is absent, when it is really present). The International Union of Pure and Applied Chemistry (IUPAC) and ISO both shy away from the words limit of detection, arguing that this term implies a clearly defined cutoff above which the analyte is measured and below which it is not. The IUPAC and ISO prefer minimum detectable (true) value and minimum detectable value of the net state variable, which in analytical chemistry would become minimum detectable net concentration. Note that the LOD will depend on the matrix and therefore must be validated for any matrices likely to be encountered in the use of the method. These will, of course, be described in the method validation document. 

The glossaries in the 1990 and 2000 Washington conference final reports [1,3] define most of the analytical terms used in the validation of a method. However, internationally accepted definitions such as those by ISO or IUPAC already exist and have been elaborated carefully over many years [2,6]. The definitions reported in the 1990 and 2000 Washington conference final reports sometime agree only partially with the ISO and IUPAC. Following are some examples for comparison. 

The ideal validated method would be the one that has progressed fully through a collaborative study in accordance with international protocols for the design, conduct, and interpretation of method performance studies. A typical study of a determinative method conducted in accordance with the internationally harmonized International Organization for Standardization (ISO)/International Union for Pure and Applied Chemistry (IUPAC)/AOAC International (AOAC) protocol would require a minimum of up to five test materials including blind replicates or split-level samples to assess within-laboratory repeatability parameters, and eight participating laboratories (15). Included with the intended use should be recommended performance criteria for accuracy, precision and recovery. 

As for all other analytical methods, methods for the analysis of products derived from modern biotechnology need to be validated. This validation should follow international standards (e.g. ISO 5725) and comply with, The IUPAC/AOAC/ISO harmonized protocol of method validation [6] or the standards cited above. Validation of testing methods is greatly facilitated by the use and availability of the appropriate reference materials. The following paragraphs specify some important... 

IUPAC method validation International Union of Pure and Applied Chemistry, Harmonized guidelines for single laboratory validation of method of analysis... 

Thomson M, Ellison SLR, Wood R (2002) International union of pure and applied chemistry, harmonized guidelines for single laboratory validation of method of analysis. Pure Appl Chem74 835-855. http //www.iupac.org/objID/Article/pac7405x0835... 

Internal QC monitors the laboratory s current performance versus the standards and criteria that have been set, normally at the time of method development or validation. To ensure that quality data are continuously produced during all analyses and to allow eventual review, systematic checks are performed to show that the test results remain reproducible. Such checks also show if the analytical method is measuring the quantity of target analytes in each sample within acceptable limits for bias (Environment Canada, 2002 IUPAC, 1995 CAEAL, 1999). 

For most regulatory applications, the method chosen will have been subjected to preliminary method development studies and a collaborative study, both carried out according to standard protocols. This process, and subsequent acceptance, forms the validation of the method. For example, the AOAC/IUPAC protocol [5, 6] provides guidelines for both method development and collaborative study. Typically, method development forms an iterative process of performance evaluation and refinement, using increasingly powerful tests as development progresses, and culminating in collaborative study. On the basis of the results of these studies,... 

The evaluation of uncertainty requires a detailed examination of the measurement procedure. The steps involved are shown in Fig. 1. This procedure involves very similar steps to those recommended in the AO AC/ IUPAC protocol [5, 6] for method development and validation, shown in Fig. 2. In both cases the same processes are involved step 1 details the measurement procedure, step 2 identifies the critical parameters that influence the result, step 3 determines, either by experiment or by calculation, the effect of changes in each of these parameters on the final result, and step 4 their combined effect. 

As of the writing of this book, claims have been put forward for the creation of elements 112,114, 116, and 118, but none of these claims have been completely validated and the 2001 claim for the discovery of 118 was later retracted by the research team. IUPAC and IUPAP (the International Union of Pure and Applied Physics) continue to oversee and adjudicate claims and in 2003 released a Technical Report saying that although many of the claims were based on good science and sound methods, there was not yet enough independent confirmation to establish priority. In the case of these elements, it is probably just a matter of time before they are officially recognized. 

Unfortunately, there is no broadly valid relation between the two quantities. The activation energies of the above chlorination reactions and analogous interactions of concern in this book have not yet been reported, and their calculation from the first principles seems difficult. Meanwhile, the above supposed chlorination steps involve atoms and molecules of lower halides - the species with unpaired electrons on an otherwise open shell configuration - which is exactly the IUPAC definition... 

Codex (2002) Codex committee on methods of analysis and sampling. In-house method validation (document CX/MAS 01/9). See also Codex committee on methods of analysis and sampling. Consideration of IUPAC guidelines for the in-house (single laboratory) validation of methods of analysis (document CX/MAS 02/10). 

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