Ruggedness, process

In summary, official German analytical methods for pesticide residues are always validated in several laboratories. These inter-laboratory studies avoid the acceptance of methods which cannot readily be reproduced in further laboratories and they do improve the ruggedness of analytical procedures applied. The recently introduced calibration with standards in matrix improves the trueness of the reported recovery data. Other aspects of validation (sample processing, analyte stability, extraction efficiency) are not considered. 

Lastly, a laboratory not involved in the development process must validate the method. The independent laboratory validation study, or ruggedness trial, ensures that analysts unfamiliar with the method can successfully perform the method. The method developer should, therefore, strive to make all procedures as straightforward as possible to aid reproducibility of the method. 

Benefits of on-line SPE include elimination of eluate collection, evaporation, and processing in a completely closed system with protection from contact with hazardous solvents, light and oxygen. On-line SPE offers ruggedness, excellent precision and high sample throughput, and is ideally suited to perform a fast matrix-analyte separation prior to e.g. LC-MS or direct MS analysis. 

The Dephy data-processing package offers several proprietary noise filtering options. We have not yet determined unequivocally whether any of these data treatments increase reproducibility or concentrate the taxonomic information content of the averaged spectra, although first results suggest that use of filtered data can improve spectral reproducibility and thus assist the ruggedness of sample classification. 

Methods can only usefully applied in analytical practice when they are sufficiently robust and therefore insensitive to small variations in method conditions and equipment (replacement of a part), operator skill, environment (temperature, humidity), aging processes (GC- or LC columns, reagents), and sample composition. This demand makes robustness (ruggedness) to an important validation criterion that has to be proved by experimental studies. The concepts of robustness and ruggedness mostly have been described verbally where it must be stated that their use is frequently interchangeably and synonymously (e.g., Hendricks et al. [1996] Kellner et al. [1998] EURACHEM [1998] ICH [1994, 1996] Wunsch [1994] Wildner and Wunsch [1997] Valcarcel [2000] Kateman and Buydens [1993]). 

Method validation is defined in the international standard, ISO/IEC 17025 as, the confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are fulfilled. This means that a validated method, if used correctly, will produce results that will be suitable for the person making decisions based on them. This requires a detailed understanding of why the results are required and the quality of the result needed, i.e. its uncertainty. This is what determines the values that have to be achieved for the performance parameters. Method validation is a planned set of experiments to determine these values. The method performance parameters that are typically studied during method validation are selectivity, precision, bias, linearity working range, limit of detection, limit of quantitation, calibration and ruggedness. The validation process is illustrated in Figure 4.2. 

Advances in instrumentation, such as diode arrays and ruggedized interferometers, have made IR and Raman instruments readily available for process work. NIR hardware has always been used more for production and quality control than laboratory and research work. They, too, have become smaller, faster, more rugged and, in 1980s dollars, less expensive. Explosion-proof enclosures allow close proximity to reactors containing solvents and can be operated in dusty locations (raw material handling situations). 

Practical FTIR solutions have been developed by paying attention to the fundamental design of the instrument. Moving an FTIR instrument out of the benign enviromnent of a laboratory to the more alien environment of either a process line or that of a portable device is not straightforward. A major emphasis on the instrument design in terms of both ruggedness and fundamental reliability of components is critical. Furthermore, issues such as enviromnental contamination, humidity, vibration and temperature are factors... 

Apart from establishing analytical validation parameters, other activities should include experimental optimization of each procedural step or method manipulation to determine the critical control steps that have a substantial impact on method performance. The ruggedness or process variability that may be employed in any particular method step, without reducing method performance, should be determined. It should be identified, for example, whether an analytical method may be stopped without adversely affecting the result. 

As is indicated in Figure 8, this process is likely to be an iterative one. However, it is essential that good written records are kept during this phase so that, in the event of problems at subsequent levels, investigations may be more readily carried out. Alas, far too often the excuse of analytical creativity is cited for lack of such records. The most important outcome from this initial evaluation should be an assessment of robustness (or ruggedness) of the developed procedure. The AO AC Guide,Use of statistics to develop and evaluate analytical methods is an excellent source for a discussion of statistical procedures for both inter- and intra-laboratory studies. 

For many years the pneumatic controller was preferred to its electronic counterpart due to its simplicity, its general ruggedness in the process environment, and the fact that its output could be used to operate directly the diaphragm of a pneumatic control valve. Although now largely superseded by software or hard wired electronic equivalents, pneumatic controllers are still employed in special circumstances, e.g. in explosive atmospheres. Furthermore, substantial numbers of pneumatic controllers can be found on older plant and thus an understanding of their principles of operation is necessary. 

Raman spectroscopy has its main strength in the combination of a fairly high chemical selectivity and a true remote sensing capability. In comparison, NIR has been used extensively in the manufacturing industry due to its ruggedness and simplicity with respect to interfacing of probes to process vessels. However, due to fairly poor spectral selectivity it has to be paired with multivariate data evaluation and is thus sometimes considered as a black box technique. Mid-IR, on the other hand, offers a high selectivity and is also well established... 

Sample Preparation/Extraction The process of separating potentially interfering components from a sample prior to LC-MS analysis for the purposes of improving sensitivity, specificity, and/or method ruggedness. Variations include solid phase extraction (SPE), liquid-liquid extraction (LLE), and protein precipitation (PPT). Extraction may be performed off-line, in which the cleanup is completely independent from the LC-MS analysis, or on-line, in which the cleanup is integrated directly into the LC-MS analysis. 

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