Human Radiolabeled Mass Balance (hAME) Studies for Regulatory Submission
Sponsored by: QPS
- Human Mass Balance
Date: 27 May
Time: 9am EDT – 15:00 CEST
Part II: Understanding Human Mass Balance and Metabolite Profiling
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.
Fred van Heuveln, PhD,
Director of Elemental Analysis
Fred graduated in inorganic and physical chemistry at the University of Groningen in The Netherlands. For over 15 years, he was involved in materials research at the Energy Center of The Netherlands and obtained his PHD in 1997. Over the last 16 years, Fred has been Head of the dedicated Elemental Analysis group, part of the QPS ICP-MS team, which has performed studies with about 40 different elements, from simple total analysis of one specific element to complex speciation studies with simultaneous analysis of free and protein bound drug compounds. Additionally, Fred is the Radiation expert at QPS Netherlands. In 2012, Fred and his colleagues published an extensive review of the QPS ICP-MS applications within drug development in the Journal ‘Bioanalysis’, click here to view: https://bit.ly/3rGdWki
Biotransformation Group Leader
Diane Grotz joined QPS, LLC in 2018 and is currently serving as Biotransformation Group Leader, in the DMPK department. In this position, Diane serves as manager of the biotransformation group, which performs metabolite profiling for in vitro, and preclinical and clinical in vivo studies. Prior to joining QPS, Diane focused on metabolite profiling as an Associate Principal Scientist at Merck (NJ, USA), and as a Senior Scientist at Schering-Plough (NJ, USA) supporting multiple therapeutic areas; also serving as Principal Investigator for discovery therapeutic teams, including responsibility for DMPK research. Diane received her Bachelor’s degree in Chemistry from Rutgers University in New Jersey, USA.
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.
- DMPK Researchers
- VPs and Directors of Clinical Research
- Drug Development Scientists
- Clinical Trials Managers
- Clinical Research Services Team Members
- Clinical Operations Team Members
- Head of Research & Development