Validation of liquid chromatography mass spectrometry (LC-MS) methods
10. Ruggedness, robustness
In this part of the course, the and are introduced and explained.
The terms robustness and ruggedness refer to the ability of an analytical method to remain unaffected by small variations in the method parameters (mobile phase composition, column age, column temperature, etc.) and influential environmental factors (room temperature, air humidity, etc.) and characterize its reliability during normal usage.
The notion of remaining unaffected by varying a method parameter has two possible interpretations – it can be interpreted as:
- (a) no change of the detected amount of the analyte in a certain sample despite of the variation of the method parameter or
- (b) no change of the critical performance characteristics (e.g. limit of quantitation) by the variation of the method parameter.
In experimental evaluation of robustness either one of these interpretations can be used.
Robustness and ruggedness definitions in the guidelines as well as review articles are very similar. Some guidelines use the term robustness and some use ruggedness. When used together these terms are treated as synonyms in most cases.
Robustness and ruggedness introduction
http://www.uttv.ee/naita?id=23686
https://www.youtube.com/watch?v=8Fpo71pUTR4&feature=youtu.be
These definitions refer to changes made to the method within the same laboratory. However, robustness can also be described as the feasibility to reproduce the analytical method in different laboratories or under different circumstances without the occurrence of unexpected differences in the obtained results or performance parameters.
Along the similar lines it has been suggested that ruggedness should be used as a parameter evaluating constancy of the results when external factors such as analyst, laboratory, instrument, reagents and days are varied and robustness should be used as a parameter characterizing the of the method with respect to variations of the internal factors of the method. This involves the parameters related to sample preparation, mobile phase composition, mobile phase flow rate, injection volume, column temperature etc. In addition, an important aspect of the robustness is the stability of the method against the variability of the sample matrix.
There are studies where the terms robustness/ruggedness are misinterpreted and actually decision threshold, detection capability or is evaluated.
In this course we use the term robustness for expressing the stability of the method against small variations of the intrinsic method parameters (section 10.1) and variability of sample matrix (section 10.2).
In this course we use the term ruggedness for expressing the stability of the method against extraneous influencing factors.
We address changes of the method parameters (i.e. within-laboratory assessment of robustness) and the variability of the sample matrices. We do not explicitly address changes occurring when a method is transferred from one laboratory to another.
