An Analytical Strategy Based on Multiple Complementary and Orthogonal Chromatographic and Detection Methods (Multidetector Approach) to Effectively Manage the Analytical Evaluation Threshold (AET)

Analytical evaluation threshold (AET): pictorial representation of the AET. An internal standard has been added to the extract at a concentration equal to the AET. When the extract is analyzed, a line at the apex of the internal standard peak is drawn horizontally across the chromatogram. Peaks whose responses are above the line must be reported for toxicological risk assessment. Peaks whose responses are below the line need not be reported for toxicological risk assessment, as they are deemed to have a negligible adverse effect on patient safety. Application of the AET in this manner is based on the assumption that the internal standard and the analytes have the same response factor. Assuming all three compounds are at an equal concentration (AET concentration), an “AET gap” is caused by differing response factors. This gap is corrected by using an uncertainty factor that takes into account response variation between analytes and internal standards. This has the effect of moving the AET line lower in the chromatogram and results in compound #1 being successfully “captured” by the AET assessment.