Robustness testing chromatographic factors

A robustness test examines potential sources (factors) of variability in one or more responses of the considered method. In pharmaceutical analysis, chromatographic and electrophoretic separation methods are most commonly evaluated. 

Table 1 gives an overview of potential factors to be considered when performing a robustness test on a capillary electrophoretic (CE) method. In references 6, 9, 17, and 19, lists of factors for high-performance liquid chromatographic (HPLC), gas chromatographic (GC), and/or thin-layer chromatographic (TLC) methods, can be found. 

THE FACTORS AND THEIR LEVELS. EXAMINED IN THE ROBUSTNESS TEST OF (82) ON A CHROMATOGRAPHIC METHOD FOR THE SEPARATION AND ASSAY OF A DRUG SUBSTANCE AND TWO RELATED COMPOUNDS IN TABLETS... 

In addition to validation of the automation, full validation of the chromatographic procedure, as described in Chapter 12, should be conducted for late-phase methods. This should include specification of system suitability parameters to ensure that the performance obtained during method development and validation is maintained during routine use. The system suitability parameters may include specification of acceptable injection repeatability, criteria for resolution between critical pairs, maximum allowable tailing factors, and a means of verifying that the requisite sensitivity is obtained. As recommended by Vander Heyden et al., system suitability limits are best set following robustness tests. 

Columns for a particular laboratory can be chosen based on some set of internal criteria. One of the criteria to select a column should be such that the column is stable for a certain number of column volumes (efficiency, tailing factor, and retention time criteria for predefined probe analytes) at the recommended maximum and minimum pH at a particular maximum temperature. This would allow the chromatographer to employ such phases with a significant degree of confidence and ensure the robustness of the stationary phase during method development and for release and stability testing. 

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