Validation trace analysis

LGC - VAM Publications (i) The Fitness for Purpose of Analytical Methods, A Laboratory Guide to Method Validation and Related Topics, (2) Practical Statistics for the Analytical Scientist A Bench Guide By TJ Farrant, (3) Trace Analysis A structured Approach to Obtaining Reliable Results By E Pritchard, (4) Quantifying Uncertainty in Analytical Measurement, and (5) Quality in the Analytical Chemistry Laboratory. LGC/RSC Publications, London, England. 

Method validation guidelines for use in trace analysis have been proposed by various authors, but there is little consistency in the recommended approaches. The general validation guidelines proposed by standards organizations such as ISO (International Organization for Standardization), DIN (Deutsches Institut fUr Normung German Institute for Standardization) and others are often not well defined and consequently... 

A final point is the value of earlier (old) validation data for actual measurements. In a study about the source of error in trace analysis, Horwitz et al. showed that systematic errors are rare and the majority of errors are random. In other words, the performance of a laboratory will vary with time, because time is related to other instruments, staff, chemicals, etc., and these are the main sources of performance variation. Subsequently, actual performance verification data must be generated to establish method performance for all analytes and matrices for which results will be reported. 

In summary, when using the indirect" technique for optical trace analysis, all of the points mentioned above have to be considered and have to be validated when setting up a standard operation procedure" (SOP), in order to conform to good laboratory practice (GLP) analysis methods. This means an extra work load compared with validation of the direct optical trace analysis procedure. Sometimes there is no way of getting round this so-called less elegant , more cumbersome and more error prone indirect technique. However, if it is performed correctly and judged critically, it is still a good method and should easily allow optical trace analysis down to 0.1% and lower. 

Computer systems validation, as established in 21 CFR Part 211.68, Automatic, Mechanical, and Electronic Equipment, is one of the most important requirements in FDA-regulated operations and an element of the system life cycle (SLC). In addition to the testing of the computer technology, other verifications and inspection activities include code walkthroughs, dynamic analysis and trace analysis. These activities may require 40% of overall project efforts. 

Computer systems validation is an element of the SLC. In addition to the software and hardware testing, other verification activities include code walkthroughs, dynamic analysis, and trace analysis. 

B. Jiilicher, P. Gowik, S. Uhlig, Assesment of detection methods in trace analysis by means of a statistically based in-house validation concept, Analyst, 123 (1998), 173-179. 

In various recent publications, the analytical method was given equal time with the validation scheme. Forbes et al. [22] presented a trace analysis method for residual isopropanol in loracarbef using NIR. The validation implications for trace analyses were examined in the paper. Trafford et al. [23] used reflectance NIR to determine the active in paracetamol tablets. Again, validation issues were discussed. 

Once a method is established, precision may be determined by suitable replicated experiments. However it is in inter-laboratory trails that the problems with environmental methods often show up. It is accepted that for trace analysis RSD values of tens of percent are likely. In studies conducted in Western Australia on pesticide residues in bovine fat RSD values for dieldrin were 12% and for dia-zonium were 28%. It is typical to see a quarter of the laboratories in such a trial producing values that could be termed outliers. In the previously mentioned study, 5 laboratories out of 26 had z> 3 for aldrin. In a parallel study RSD values for petroleum in dichloromethane and water were 40% and 25%, respectively. The conclusions of these studies was that there was poor comparability because of the different methods used, that accreditation apparently made no difference to the quality of results, and that a lack of understanding of definitions of the quantities to be analysed (for example gasoline range organics ) caused non-method errors. In relation to methods, this is contrary to the conclusion of van Nevel et al. who asserted that the results of the IMEP round of analyses of trace elements in natural and synthetic waters showed no dependence on method [11]. If properly validated methods do yield comparable results, then one conclusion from the range of studies around the world is that many environmental methods are not validated. It may be that validated methods are indeed used, but not for exactly the systems for which they were validated. 

Trace analysis and the move to the use of smaller sample sizes represent particular challenges in that the ratio of surface area exposure to sample volume, or quantity of analyte, is increased, multiplying the possible effect and level of contamination. While mass spectral identification of contaminants will aid in identifying their source (see the literature-derived Excel database of contaminant mass spectra in the supplementary data of Keller et al 12), this is not essential. The key tool to their elimination is the appropriate use of sample blanks at each step of the analytical protocol during method development and validation. 

G Singh, V Arora, PT Fenn, B Mets, IA Blair. A validated stable isotope dilution liquid chromatography tandem mass spectrometry assay for trace analysis of cocaine and its major metabolites in plasma. Anal Chem 71 2021—2027, 1999. 

For a well resolved peak, its area as well as its height is proportional to the amount of analyte. Therefore, one can choose between these two possibilities. Perhaps area determination is more precise but this should be tested during the validation of the method (Section 20.3). If the signal-to-noise ratio is small, then area determination is a difficult task for the integrator and so it is better to use quantitation by height for trace analysis. 

Sensitivity is mainly a limiting factor in trace analysis. It is evident that the method applied should be sensitive enough so that the concentration of substance to be determined is accessible (limit of detection and determination) or the colonies of microbes countable. It must also deliver a measurable difference for a small change in content. When the sensitivity of the method of final detection is a limiting factor the analyst may have several possibilities which all will influence the selection, optimisation and validation of the other steps of the procedure. He may ... 

To better understand the step-wise approach for method development and validation, it is necessary to give examples. They are taken from organic and inorganic trace analysis of environmental matrices. Figure 2.2 illustrates the steps for the validation of the analytical procedure for the determination of polychlorobiphenyls (PCB) in industrially contaminated soil. Figure 2.3 shows the steps necessary to validate the determination of trace elements and particularly arsenic in a fish tissue. Each step of the procedure will provide the necessary information so that the next step can be done with confidence. In practice, the analyst will develop a procedure to quantify all primary and secondary method characteristics as defined in section 2.1.4. 

It is possible to produce artificial matrix materials [12]. Such materials can be prepared on a mass basis by weighing all components both to mimic the matrix composition and the content of trace elements or trace organic substances. The materials could help to have matrix materials available for which the exact contents and composition are known. As a consequence it would be, in theory, possible to certify them on a mass basis and validate methods with highly traceable materials. In organic trace analysis this would circumvent the unknown extraction step. In reality, this is much more difficult to achieve than can be expected. The real matrix composition of many materials is unknown — in particular for environment samples. The physico-chemical status of the various substances depends on the history of the material. Therefore, various natural samples of expected similar composition are different in behaviour. In addition, when preparing mixtures of solid components, losses cannot be excluded and unfortunately are not quantifiable. Attempts have been made where losses were demonstrated but not quantified [12]. Therefore, materials certified for matrix composition and analyte content on a mass basis do not yet exist or are not of real use for method validation by routine laboratories. They may be of interest for laboratories active in the field of fundamental research in chemical metrology where smaller quantities of material are handled. 

For trace analysis it is necessary to use the most sensitive methods. If the selectivity of the most sensitive method is not great enough it is necessary to validate using tandem techniques, which entail a separation step before the analysis itself. 

Recently, Psillakis et al. " have developed a liquid phase microextraction (LPME) technique using a hollow fiber membrane in conjunction with GC-MS for the extraction and analysis of phthalates. The resulting method was validated and compared with SPME. Both techniques showed comparable performance and were considered suitable for trace analysis of phthalates in water. 

If data of the real system is available, the developed simulation model can be tested for similarity with the real system in a qnantitative way (bottom-right cell in Table 4.8). For this purpose, a lot of statistical procedures can be applied depending on the specific object to be tested. Typically, regression techniqnes, distribution tests, or time series analysis methods are used. A reliable qnantitative approach is to generate a forecast of the near future by means of the simulation model which is then compared with the real systems behaviour after the forecast period has expired. This is called predictive validation A mixture of trace analysis and fixed-value test is the trace-driven simulation where a historical situation is simulated. The model s output is compared with the historical records then. 

Making quantitative measurements is always accompanied by errors and necessitates an understanding of detectors (see Chapter 7) and data systems (see Chapter 2). Sampling, sample preparation, instrument and method validation, and quality assurance are all important parts of the process. Trace analysis, which is becoming increasingly popular, requires that all... 

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