Robustness automated methods

Rozenman, Y. and Di Bussolo, J. M., Developing Robust HPLC Separations Using an Automated Method Development System, Pharm. Tech., 10-19, 1998. 

Robustness. Examples of typical possible sources of variation in automated methods are homogenization speed, homogenization time, age of sample, accuracy of solvent dispense, and temperature variation. If all studies described in the method development have been performed, the robustness of the sample preparation has been demonstrated and does not require additional testing. Parameters in relation to the measurement technique may need to be considered and are covered in the relevant chapter. 

The key to successful integration of automation into the modem analytical laboratory is a sound approach to method development and validation. The end result of a well-developed and validated automated method will be a robust analytical method that should pay dividends by being able routinely to produce sound analytical data to support crucial regulatory submissions. 

The first requirement for development of CSDSymmetry is a robust and automated method for analysing exact and approximate molecular symmetry. The specific methodology that has been employed is a combination of checks for topological equivalence in the 2-D connectivity diagram followed by full 3-D symmetry perception [29]. The first part of the process is based on the fact that atoms related by symmetry within a molecule must have identical chemical environments - that is, symmetry-related atoms... 

To obtain the best from an automated analysis, it is important that only a robust manual method is considered for automation. To use automation effectively, the following factors should be considered before attempting any work on a method. 

Time The time available can often determine the approaches taken in method development therefore, it is important to use time effectively and plan the work well. Such constraints may not always be compatible with the development of automated methods. Again this emphasizes the need for a robust manual method to be selected for automation. 

The determination of acesulfame-K, cyclamate, and saccharin individually or simultaneously with other artificial sweeteners and/or other food additives in foods, soft drinks, and tabletop sweeteners is very important for legal, health, and consumer safety aspects. Thus, reliable, simple, fast, sensitive, accurate, and robust analytical methods using low-cost equipment are essential to protect human health, meet the requirement to ensure product quality, and support the compliance and enforcement of laws and regulations pertaining to food safety. Flow analysis is shown to be a powerful analytical tool for the automated determination of acesulfame-K, cyclamate, and saccharin in food samples, and it is an interesting alternative for use in sweetener determinations when only one analyte is determined in a large number of samples. In the last few years, flow analysis... 

In the past decade, new sample extraction techniques have been introduced to meet stricter criteria in the areas of food and agriculture, for example, enviromnentally friendly, non-toxic, fast, automated, robust, and cost-efficient techniques. Accelerated solvent extraction (ASE) and pressurized liquid extraction (PEE) are two methods developed for the extraction of chemicals of interest " and provide high yields and efficiency from a wide range of botanical, - animal, and biological samples. ASE and PLE combine solvents at elevated temperatures (40 to 200°C)... 

Owing to its potential of performing extremely high-efficiency separations, robustness of the equipment, automation, ease of use and flexibility, electromigration methods, i.e. CE have widely been applied to different problems in analytical chemistry. It is considered to be a complementary or even an alternative technique to established chromatographic techniques such as HPLC, GC and others. 

When performing dissolution testing, there are many ways that the test may generate erroneous results. The testing equipment and its environment, handling of the sample, formulation, in situ reactions, automation and analytical techniques can all be the cause of errors and variability. The physical dissolution of the dosage form should be unencumbered at all times. Certain aspects of the equipment calibration process may show these errors as well as close visual observation of the test. The essentials of the test are accuracy of results and robustness of the method. Aberrant and unexpected results do occur, however, and the analyst should be well trained to examine all aspects of the dissolution test and observe the equipment in operation. 

The method is extremely robust and reliable and obeys the Beer-Lambert relationship to a final protein concentration of about 2 g 1 1 (a sample concentration of about 20 g l-1) with a lower limit of about 100 fig of protein (sample concentration of 1.0 g l-1). The colour reaches maximum intensity in about 15 min and is stable for at least several hours. The method is simple and reliable and readily lends itself to automation but its lack of sensitivity is its greatest drawback. All proteins react in a similar manner and results show very little difference for different proteins. 

With the advent of API sources, LC/MS/MS allows the facile development of quantitative methods that are sensitive, selective, robust, and amenable to the rapid analysis of a majority of small molecules. In order to achieve high-throughput bioanalysis in support of pharmacokinetic studies, many approaches have been reported utilizing automated sample preparation and reducing analysis time by pooling samples, parallel analysis, and fast chromatography. 25,26,152,153... 

Preconcentration can enhance instrumental detection Hmits by two orders of magnitude. Interfering sample components (i.e. high salt contents) are readily removed. The commercially available TraceCon system provides a simple automated step for combining flame-AAS or ICP-OES analytical methods. Its robust design shows many good aspects of laboratory automation. 

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