INVESTIGATION OF ROBUSTNESS AT VALIDATION OF HPLC AND UPLC METHODS: A MODERN APPROACH INCLUDING RISK ANALYSIS

Abstract

A new approach to the robustness investigation of HPLC/UPLC methods that includes use of risk analysis is offered. It allows reliable justification of the choice as well as omission of certain factors at study of the robustness of HPLC/UPLC methods. The risk level of factors is determined using a special matrix and a table to assess the сriticality of the factor and the рrobability of its critical impact on responses. It is emphasized that the exclusion of any factor associated with the chromatographic system from investigation of robustness at validation of a concrete method has to be reliably justified - with the use of a risk analysis including consideration of the features of chromatograms and theoretical arguments. For the factors that often have the high and average level of risk, we provide and discuss the guide values for the limits of the factor change based on our own experience and literary data. We also suggest the guide values for permissible limits of the responses variation as well as an example of assessment of robustness of the method for determining impurities using risk analysis and «оne-factor-at-a-time» method. Recommendations are made to study of the robustness of HPLC/UPLC methods.