Mass Balance, Excretion and Expired Air Collection
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Mass balance studies — also known as C-14 studies or Absorption, Metabolism, and Excretion (AME) studies — are critical for understanding the complete disposition of a drug in the body. By quantifying how much of an administered dose is absorbed, metabolized, and ultimately excreted, these studies provide a holistic view of a compound's pharmacokinetic fate.
A well-designed human or animal mass balance study helps to:
- Determine the overall mass balance of drug-related material after dosing.
- Quantify the ratio of parent drug to metabolites in circulation.
- Identify the primary route(s) of excretion, including urine, feces, bile, or expired air.
- Characterize major and minor metabolites for safety and regulatory evaluation.
In a mass balance study, the test article is typically labeled with a radioactive isotope, most often 14C or 3H. Urine, feces, bile and expired air (collectively, excreta) are assayed following administration of the labeled compound to confirm that essentially 100% (usually >90%) of the administered radioactivity is recovered. This enables accurate characterization of absorption, clearance and metabolic pathways both in preclinical species and in humans.
Our Comprehensive Research Content
- Radioisotope Administration
- Species and Model Selection
- Sample Collection & Processing
- Analytical and Detection Methods
Radioisotope Administration
Radiolabeling:
Radiolabeling enables precise tracking of both parent compound and metabolites. Available isotopes include:
3H, 14C, 32P, 35S, 125I (additional isotopes available upon request).
Dose Administration:
The radiolabeled compound is administered to preclinical species or human subjects using a dosing route that reflects the intended clinical use. Supported administration routes include:
Oral, Intravenous, Subcutaneous, Intramuscular, (Trans)dermal, Inhalation, Intradermal / Transdermal, Oropharyngeal, Intraduodenal, Intraperitoneal, Intranasal, Continuous infusion, Ocular
Species and Model Selection
We conduct mass balance and excretion studies across standard preclinical species, including:
- mouse, rat, dog, and non-human primate (NHP).
- Customized models are available upon request for specialized compound classes or therapeutic areas.
Sample Collection & Processing
- Excretion Collection: Comprehensive, quantitative collection of urine and feces is performed over a sufficient period (typically 7–10 days, or until >90% recovery is achieved).
- Expired Air Collection: For volatile compounds or those expected to metabolize into CO₂, we utilize metabolic cages or whole-body collection systems to capture and quantify ¹⁴CO₂ using alkali trapping techniques.
- Other Matrices: Plasma, whole blood, bile (via catheterization in preclinical models), and tissue samples (for Quantitative Whole-Body Autoradiography, QWBA) are collected according to study protocol.
Analytical and Detection Methods
- Radioanalysis: All biological samples are homogenized and analyzed via Liquid Scintillation Counting (LSC) to determine total radioactivity.
- Metabolite Profiling: Samples are further analyzed via radio-HPLC (High-Performance Liquid Chromatography coupled with in-line radiometric detection) to separate, profile, and quantify individual metabolite fractions.
- Metabolite Identification: Structural elucidation of major metabolites is achieved through techniques like LC-MS/MS (Liquid Chromatography with Tandem Mass Spectrometry) and NMR.
Our Service Excellence and Differentiating Capabilities
Customized Study Design
Optimized dosing routes, isotope selection, and matrix collection strategy to fit study objectives.
High Recovery Assurance
Full urine, feces, bile, and expired air collection for up to 14 days to ensure ≥ 90% recovery.
Regulatory Confidence
Study directors with proven experience and a SOP library that minimize data gaps and regulatory queries.
Advanced Analytical Workflows
Fully integrated radiometric and LC-MS/MS platforms for robust metabolite characterization.
Integrated ADME Platform
Fully connected Mass Balance, Metabolite ID, QWBA, and Absolute Bioavailability studies for an integrated development workflow.
FAQ
At what stage of development should the Mass Balance study be performed?
Human radiolabeled mass balance studies are typically performed relatively early in clinical development, ideally before the commencement of Phase III trials. Early information on metabolite exposure and clearance pathways is critical for selecting appropriate dosing and patient populations in subsequent studies.
Why is the recovery target important?
The >90% recovery is an important quality measure indicating that the majority of administered dose has been accounted for. Failure to meet this target can trigger regulatory queries to ensure that the drug is not being retained or irreversibly binding to tissue, and that there is not an uncharacterized elimination pathway (e.g. a highly volatile component).
How do you know if expired air collection is necessary for my compound?
A detailed pre-study review of your compound's structure is conducted. If the compound contains aliphatic chains, or other heterocyclic rings and functional groups (e.g. tert-butyl) that are known to be cleaved from the parent compound and metabolized to CO2, we will recommend including expired air collection.
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