An hAME study typically covers two analyses for mass balance, 1) before dosing: the analysis of the formulation and dosing samples, and 2) after dosing: the analysis of the human blood, plasma, feces, and urine samples. Mass balance determines the amount of radioactivity dosed to the subject compared to the amount excreted. This main analytical objective determines the excretion and clearance profiles for total radioactivity in blood, plasma, urine and feces. Another objective is to determine the recovery values (percentage of the dosed radioactivity) which, in relation to the discharge criteria, define when subjects are allowed to leave the clinic
Subsequent to mass balance analysis, the samples are analyzed for metabolic profiling. Understanding the human metabolic profile is a critical part of a regulatory package in support of new drug applications. Metabolite profiling elucidates major metabolic pathways, as well as identifies and quantifies metabolites and their relative proportion resulting from the administered radiolabeled drug. Samples are profiled using selective chromatographic methods and high-resolution mass spectrometry to separate metabolites from the unchanged drug. The metabolites are characterized and potential structures are proposed. Finally, all radiolabeled peaks (unchanged drug and metabolites) are radio-quantitated to calculate the ratio of quantifiable metabolites to parent and the overall exposure of the subjects to the drug and its metabolites.
This webinar will examine the typical mass balance aspects of formulation and study sample analysis as well as some general aspects for working with radioactivity. Also discussed will be understanding how metabolite profiling supports regulatory filings and future clinical studies.
Key Learning Objectives
- Typical analytical aspects of a formulation analysis in relation to an hAME study.
- Analysis of human study samples to determine the recovery of a radioactive labeled drug in an hAME study.
- Determination of the exposure of unknown metabolites as proportion of drug-related material.
- Comparison of metabolic profiles to provide crucial information for your toxicological studies.
