Cross validation of Endogenous assays

Use of Non-chromatographic techniques for Bio-analysis

ISR involving multi-analyte methods. Is there any need for a separate Sample Selection, in case of
multi-analyte assays?

Abstract: There is overall consensus on the need for Incurred sample re-analysis in regulated Bioanalysis across the Industry and regulatory agencies. Some of the issues with respect to percentage of samples to be repeated and the acceptance criteria are addressed in white paper and crystal city meetings. With 5 % to 10 % benchmark for ISR sample repetition, in case of multi-analyte assays, percentage of samples repeated tends to be in excess of 20 % of total sample. Here we are presenting a case study involving an analyte and two of its active metabolite, which can be used to demonstrate that if the dynamic range for the assay of all three analytes are of the same magnitude and if the values of t_max are close (within 3 to 4 hrs of parent) for all three analytes, the corresponding values for the two metabolites, from the samples selected for parent analyte should suffice to establish the incurred sample reproducibility for all the three analytes. This approach would reduce the percentage of samples to be re-analysed for ISR by almost 2/3. Also this would be more logical in the sense that we would be picking samples for metabolite randomly rather than choosing those specifically near C_max.