Human mass balance studies with unparalleled sensitivity
Leverage the unique sensitivity of Accelerator Mass Spectrometry (AMS) to accelerate your clinical program. Obtain definitive human ADME data from Phase 1 by reducing radiation exposure.
Redefining hADME Programs
Human mass balance studies are a regulatory requirement for characterisation of the clearance pathways and metabolic profile of a new drug. Traditional methods often require late-stage execution due to high radioactive doses. Application of a conventional radioactive dose of 100 uCi or higher is not considered ethical for early-stage human studies (Ethics ICRP 62). This results in the risk of late-stage findings of unexpected human unique metabolites that require additional nonclinical or additional work. Earlier metabolite profiling gives the team time to mitigate risks before the issue reaches the critical path.
Peregrion’s microtracer approach enables the integration of human mass balance studies into early Phase 1 trials. By using ultra-low 14C doses, we minimize exposure of healthy participants, allowing definite mass balance data to be generated months, or even years, ahead of traditional timelines. As a benefit, for instance, renal impairment studies can be waived if it is shown that the drug is not cleared via the kidney. QWBA studies and dosimetry calculations can be eliminated at this stage.
You will receive: human mass balance data (% recovered), urine versus feces excretion (%), PK profile in plasma and whole blood, AUC, t1/2.
We also offer: trial participant screening prior to the start of the study, sample preparation including feces homogenization.
The unparalleled sensitivity of AMS-enabled mass balance studies provides the solution for your program
Compounds with long half-life
The compound has a half-life of multiple days requiring high detection sensitivity.
Compounds with low bioavailability
A minor fraction of the compound enters the bloodstream and therefore extreme sensitivity is needed to detect levels in plasma and whole blood.
Compounds that are slowly excreted
Conventional high radioactive doses are non-ethical when parent drug and its metabolites are slowly excreted.
Any small molecule or peptide
Early AMS studies clarify clearance routes and identify long-lived metabolites, supporting the design of DDI and impairment studies.
Practicalities of the human mass balance study
| Parameter | Peregrion AMS Approach | Client Benefit |
|---|---|---|
| Typical cohort size | 6-8 participants | limited number of participants |
| Sample matrices | whole blood, plasma, urine, feces, exhaled air, bile and vomit | direct measurement, no sample preparation needed |
| Sample volume required | 5 uL plasma or whole blood | very small volume needed |
| Analysis speed | sample analysis on AMS takes only 8 mins | many samples in a short amount of time |
| Sensitivity range | LLOQ of 1-10 mBq/ml, which is 500-10,000x lower than LSC | applicable for low dosage drugs, drugs with long half-life, long living metabolites, drugs with slow excretion |
| Radiation dose | ≤ 1 µCi; 100-1,000 lower than conventional studies | studies are approved as early as Phase 1, as the radiolabeled product falls in ICRP Class I |
| Analysis speed | sample analysis on AMS takes only 8 minutes | many samples in a short amount of time |
| Duration until reporting | within 48 hours of sample receipt | rapid data for discharge studies |
Combined TRA & metabolite profiling in one study
Extend your total radioactivity analysis to obtain metabolite profiles including metabolite identification. Integrated results are generated from a single injection by coupling UPLC-hrMS + AMS systems.
Benefits of combining studies
- Full mass balance and metabolite data package from a single sample
- 100% match between metabolite identification and quantification
- Decreased interindividual variability
- Excretion results can be directly coupled to the metabolite profile
Why Peregrion's AMS-enabled services for mass balance determination
Guided by Scientific Experts
Sabrina Hanswijk
Sabrina has a background in biomedical sciences and holds a PhD in neuroscience. She has 5 years experience as a scientist in AMS with her main focus on mass balance and absolute bioavailability studies.
Ioana Barbu
Ioana has a background in analytical chemistry and physics and holds a PhD in mass spectrometry. She has 5 years experience as a scientist in AMS with her focus on metabolite profiling/identification, mass balance and absolute bioavailability studies
Vivian Ogundipe
After finishing her Master’s degree in biomedical sciences, Vivian successfully completed her PhD in biological and biomedical sciences. Since then, Vivian has worked as a Project Manager for AMS-related studies.
What do others say about us
“I consider Peregrion as a great option for future mass balance studies, based on my experience with acoziborole, which received an EMA positive opinion for the treatment of sleeping sickness in February 2026. The mass balance study conducted with TNO, of which Peregrion is a spin off, was part of the package that was submitted to health authorities and very much helped in the discussion of the drug label with them.”
Jean-Yves Gillon PharmD, PhD
Related Services
Absolute Bioavailability
Information on absolute bioavailability can help interpret mass balance data and understand the overall drug elimination pathways. For instance, if a large fraction of the drug is found unchanged in feces, bioavailability data supports understanding of the role of biliary and/or gut wall secretion to drug elimination.
Metabolite Profiling
Information on absolute bioavailability can help interpret mass balance data and understand the overall drug elimination pathways. For instance, if a large fraction of the drug is found unchanged in feces, bioavailability data supports understanding of the role of biliary and/or gut wall secretion to drug elimination.
Metabolite Profiling
Information on absolute bioavailability can help interpret mass balance data and understand the overall drug elimination pathways. For instance, if a large fraction of the drug is found unchanged in feces, bioavailability data supports understanding of the role of biliary and/or gut wall secretion to drug elimination.
Feces homogenization
Information on absolute bioavailability can help interpret mass balance data and understand the overall drug elimination pathways. For instance, if a large fraction of the drug is found unchanged in feces, bioavailability data supports understanding of the role of biliary and/or gut wall secretion to drug elimination.
Resources & Publications
New publication on a long-duration microtracer ADME study of osivelotor
A newly published Phase 1 study shows how microtracer dosing and AMS enabled the characterisation of osivelotor’s mass balance and…
New publication on xevinapant absolute bioavailability and human ADME
A Phase 1 study on the absolute bioavailability, pharmacokinetics, metabolism and excretion of xevinapant has been published open access in…
New publication on the human ADME and metabolite profile of camizestrant
A newly published Phase 1 study shows how AMS enabled total-radioactivity analysis from 5 µL samples and detailed metabolite profiling…
AMS Microtracer Studies in Early Drug Development: Wouter Vaes on the Clinical Pharmacology Podcast
AMS microtracer studies let teams generate human ADME and mass balance data early in clinical development, while there is still time to…
Support
FAQs
How do I start a microtracer study with Peregrion?
That’s easy. Contact us via the Contact Page on the website or reach out to your existing contact person at Peregrion. After initial exploratory conversations, we can arrange a CDA to freely talk about the project and your needs, and suggested steps forward. Our scientists will be involved at an early stage to develop optimal study designs. After submission and approval of our proposal we will agree on a Study Agreement or Master Services Agreement. Your dedicated Project Manager will then guide you through the practicalities of getting started. When there is clarity on the dosing date(s) we will reserve time slots in our facility. You can contact us any time, we are happy to help.
What type of excreta are used in radiolabeled studies?
Total radioactivity measurements are done with human plasma, urine, whole blood, feces, exhaled air, bile and vomit. Very low sample volumes are required, i.e. 5 uL of plasma for a total radioactivity analysis and 50 uL of plasma for the generation of PK data or metabolite profling data. Samples are introduced via an automated sample combustion device that generates CO2, which is directed to the AMS via an interface. A single sample is completed in less than 10 minutes. The speed of the analysis supports discharge studies from a clinical site. You will receive the study results within 48 hours after sample receipt.
Which data can be generated with Peregrion’s AMS-enabled studies?
- Absolute bioavailability data
- PK profile (for parent drug and known metabolites)
- Metabolite profile including metabolite identification
- Mass balance data
- Routes of excretion
- Information on the first pass effect
- Fraction absorbed
- Volume of distribution
What is a microdosing study in the context of a microtracer study?
A microdosing study includes a very low dose of the drug product (e.g. 100 µg) with a 14C microtracer. Due to the low dose (considered as an impurity) there is no toxicological concern and only a limited pre-clinical package is required to conduct such a study. This comes with the advantage that fewer lab animals are needed. Multiple drugs can be administered in the same study in parallel groups to aid in PK based candidate selection. A typical microdosing study consists of approximately 6 volunteers per drug. The microdose can be administered via any route, e.g. oral or intravenous.
Is human ADME data that is generated with microtracer studies acceptable for regulatory submissions?
The answer is ‘Yes’. We deliver data to our clients to support their regulatory submissions with regulatory-required or requested data such as human metabolism, routes of excretion, absolute bioavailability, and fraction absorbed. The FDA guideline on Safety Testing of Drug Metabolites Guidance for Industry (CDER) March 2020 Pharmacology/Toxicology recommends performing human in vivo metabolic evaluation as early as possible. The level of radioactivity in a microtracer study is only 0.1-1µCi. Conventional studies generally apply 100µCi. Due to the 100-fold lower radioactivity levels, ethical committees approve the use of 14C microtracers in early stage clinical development.
Why is 14C labeling required for safety studies?
Incorporating radioactivity in the drug molecule is needed to ascertain that all metabolites will be found in the systemic circulation. Since virtually all drugs contain carbon, the highest scientific standard practice is to synthesize the drug with incorporation of radioactive carbon-14, and to dose this radioactive material to a small number of healthy participants or patients in a hADME study. Samples from excreta and blood or plasma can be analyzed to trace the drug and its metabolites. Analysis via AMS is up to 10,000-fold more sensitive than classical methods, for instance Liquid Scintillation Counting (LSC) and therefore very small amounts of radioactivity are sufficient.
What are the combined advantages of microtracer studies in clinical development?
Overall, the microtracer-based mass balance, metabolite profiling and absolute bioavailability studies in early clinical developments give an enormous enrichment of the data package available at early stage without the need for separate studies to determine human ADME data. The data richness allows better study designs for follow up clinical studies, it allows earlier assessment and risk mitigation strategies for unexpected human unique metabolites, and it eliminates the need to conduct radioactive animal mass balance/metabolite profiling studies, where many animals, and much time and money are being spent on non-relevant animal metabolites.
