Method development data handling

A critical attitude towards the results obtained in analysis is necessary in order to appreciate their meaning and limitations. Precision is dependent on the practical method and beyond a certain degree cannot be improved. Inevitably there must be a compromise between the reliability of the results obtained and the use of the analyst s time. To reach this compromise requires an assessment of the nature and origins of errors in measurements relevant statistical tests may be applied in the appraisal of the results. With the development of microcomputers and their ready availability, access to complex statistical methods has been provided. These complex methods of data handling and analysis have become known collectively as chemometrics. 

ESR Spectroscopy. Electron Spin Resonance spectroscopy is an important technique for investigating the role of radical intermediates in radiation chemistry. The technique has been used widely for many years in the study of radicals occurring in irradiated solid polymers (.6,7). However, by their very nature, such species are reactive and may only exist in low concentration. The identification of these species can also be a problem since in the majority of polymers the environment of the radicals leads to broad, unresolved ESR spectra, which makes detailed spectral analysis difficult. In recent years, many of these problems of sensitivity and resolution have been reduced by more sensitive and stable ESR spectrometers and by development of new methods of data handling and manipulation. 

Chemistry, like any scientific discipline, relies heavily on experimental observations, and therefore on data. Until a few years ago, the usual way to publish information on recent scientific developments was to release it in books or journals. In chemistry, the enormous increase in the number of compounds and the data concerning them resulted in increasingly ineffective data-handling, on the side of the producers as well as the users. One way out of this disaster is the electronic processing, by computer methods, of this huge amount of data available in chemistry. Compared with other scientific disciplines that only use text and numbers for data transfer, chemistry has an additional, special challenge molecules. The molecular species consist of atoms and bonds that hold them together. Moreover, compounds... 

Hyphenated analytical methods usually give rise to iacreased confidence ia results, eaable the handling of more complex samples, improve detectioa limits, and minimi2e method development time. This approach normally results ia iacreased iastmmeatal complexity and cost, iacreased user sophisticatioa, and the need to handle enormous amounts of data. The analytical chemist must, however, remain cogni2ant of the need to use proper analytical procedures ia sample preparatioas to aid ia improved seasitivity and not rely solely on additional iastmmentation to iacrease detection levels. 

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. 

Work by Catanzaro et al. in 1968 (6) led to a new analytical procedure permitting the measurement of isotopic ratios to about 0.05% (95% L.E.) this resulted in the availability of three standard reference materials, so that results could be placed on an absolute basis. This procedure, still the most precise and accurate one available, requires about 1 mg of lead for an analysis. A second procedure (7) has been developed which utilizes silica gel as an ionization enhancer. This method permits the measurement of isotopic ratios to about 0.1% (95% L.E.), but it requires only 0.1 /xg of lead per analysis. In addition, the instrumentation and data handling have been vastly improved so that many samples can be studied quickly and conveniently. 

Even though the attention of scientific literature to TLC methods has decreased steadily over the past few years, TLC is still a routinely used analytical technique, especially in developing countries. Improvements in the technique includes the use of a microcomputer interfaced with a fluorodensitometer to simplify data handling (28). 

A significant portion, as high as 70% with new tools, of research time is dedicated to purely methods development. Methods development is necessary, as polymer chemistries, properties, and applications are extremely diverse. A portion of this methods development is focused on how to handle different materials, such as butyl rubber versus low-density polyethylene. However, the largest portion of methods development is dedicated to data correlation. 

The method development process will be aided if we are able to use sophisticated instrumentation (see also section 1.7.2). Automated injection and data handling will allow a number of experiments to be performed without the requirement of an analyst being present. Moreover, we have seen in chapter 5 (section 5.6) that the use of sophisticated detection techniques (dual-channel or multi-channel detectors) may be of help in the optimization process. 

Chapter 6 describes the computer methods developed by Dr. Roger Staden at the MRC Laboratory of Molecular Biology, Cambridge, for handling the sequence data produced by the rapid shotgun sequencing techniques described in Chapter 4. Since... 

It is essential to develop a quality assurance (QA) programme that covers sample collection, sample handling, and methods for on-site and laboratory analysis, data handling and record keeping. The QA programme should address the variety of different scenarios likely to be encountered. Appropriate calibration and analytical... 

Many advances have been made in recent years in chromatographic instrumentation and data handling including important advances in automation. However, for many methods, equally important is the sample preparation procedure. These are sometimes complex, and are often the key step in a method, but perhaps receive less attention than is warranted. The optimisation of sample preparation and the development of... 

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