Evaluation of the uncertainty of a quantitative approach to drug metabolites in the absence of authentic standards

[...]a metabolite profile should be investigated during clinical studies. [...]it is very challenging to assess the quantitative profile of a metabolite without an authentic standard. Despite these ad-hoc rules, there has not been enough discussion when it comes to evaluating the results of the preliminary and semi-quantitative assays. Because of the nature of the current accuracy and precision criteria that are used in a regulatory standard, the application of further ad-hoc criteria lacks scientific credibility. Because the radioactivity per molecule is consistent among metabolites and their unchanged drugs, the UV response factor of metabolites be calibrated by comparing HPLC-UV and HPLC-radioactivity detector (RAD) chromatograms.