Robustness testing investigated

A tentative list of factors that may be investigated in the robustness test is presented in Table 8. This list is not complete and additional factors may be added. The limits for the factor levels are proposals and should be evaluated case by case. The significance of the effects of the factors on the responses such as the resolution of all peak pairs, the tailing factor, retention times, analysis time, etc., is evaluated. 

Table 1 also contains some peak measurement/analysis parameters that might be investigated in a robustness test (see Section III.C). ° However, except from the detection wavelength, these parameters are hardly ever evaluated in a robustness test, even though they can have a large influence on the electropherogram. 

TABLE 2 Factors and Their Levels Investigated in the Robustness Testing of the Chiral Separations of Propranolol, Praziquantel, and Warfarin ... 

A simple example, focusing on the analytical procedure, will illustrate the type of experimental design used to investigate three key factors in an HPLC method. Detailed discussion of experimental designs for robustness testing can be found in Morgan and Hendriks et Riley and Rosanske provide an... 

TABLE 2.4. Factors and their levels investigated in a robustness test on a CE method to determine rufloxacin hydrochloride in coated tablets (29)... 

Another important aspect in validation of a new dissolution method is to investigate how sensitive the dissolution results of the product, for which the method has been developed, are for minute variations in operating conditions. Examples of factors to consider in such a test are temperature of test medium, rotational speed, volume, sampling procedure, medium compositions and testing performed by different operators. Based on such robustness tests of the method, limits can be defined for acceptable variations of test conditions. Statistical design may be useful to apply in situations such as those demonstrated earlier in this chapter. 

The robustness-test of a quantitative off-line OPLC assay-procedure was recently reported (89). The test was performed by fractional factorial design and evaluated by half-normal probability plot. The effects of seven factors were investigated on two levels. The method was found to be robust. 

It is an unquestioned objective of the robustness test using statistical experimental design (DoE = Design of Experiments) to perform a systematic investigation of the connections between target values y and factors x, %2,. .. x with very few experiments. In most cases, these can be adequately described by a linear model (plan of first order) ... 

For the reasons described, no specific test will be advanced here as being superior, but Huber s model and the classical one for z = 2 and z = 3 are incorporated into program HUBER the authors are of the opinion that the best recourse is to openly declare all values and do the analysis twice, once with the presumed outliers included, and once excluded from the statistical analysis in the latter case the excluded points should nonetheless be included in tables (in parentheses) and in graphs (different symbol). Outliers should not be labeled as such solely on the basis of a fixed (statistical) rule the decision should primarily reflect scientific experience. The justification must be explicitly stated in any report cf. Sections 4.18 and 4.19. If the circumstances demand that a mle be set down, it is best to use a robust model such as Huber s its sensitivity for the problem at hand, and the typical rate for false positives, should be investigated by, for example, a Monte... 

The experiments conducted to perform ruggedness tests of measurement procedures can also be viewed as experiments to investigate robust design see, for example, Wemimont [2], and Youden [3,4]. The objective of ruggedness tests is to determine a robust measurement procedure that is a procedure that will give a consistent (and correct) result under a range of measurement conditions. 

Therefore the influence of temperature and humidity on the robustness will be investigated. The maximum number of alkaloids to be separated in the paper of Coenegracht et al [3] was six in opium, and the separation of seven alkaloids in this paper is a severe test of the four solvent systems suitability for the separation of alkaloids. The alkaloids are strychnine, quinine, narceine, heroin, noscapine, caffeine and papaverine. 

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