Excretion studies are a fundamental component of ADME (Absorption, Distribution, Metabolism, and Excretion) assessment in early drug discovery and development. Understanding the routes and rates of drug elimination, whether via urine, feces, bile, or expired air, is essential for elucidating the pharmacokinetic profile of a candidate molecule. BOC Sciences provides comprehensive excretion study services designed to determine the mass balance, identify major elimination pathways, and characterize metabolite excretion profiles. Our non-regulatory, R&D-focused services utilize advanced LC-MS/MS and radiolabeled (14C/3H) techniques to provide precise data, helping clients optimize molecular structures and de-risk compounds before advancing to later development stages.
We conduct rigorous mass balance studies to account for the total recovery of the administered dose. By quantifying the parent drug and its metabolites across all excreta, we help researchers understand the complete fate of the molecule and ensure no significant bioaccumulation occurs.
Our team determines the primary routes of excretion (renal vs. biliary/fecal). We employ specialized models, including bile duct cannulation, to distinguish between unabsorbed drug and drug excreted via the bile, providing critical insights into bioavailability issues.
We analyze the rate of excretion over time to determine elimination half-life and clearance mechanisms. This kinetic data is vital for predicting dosing intervals and understanding the potential for drug-drug interactions (DDIs) involving transporters.
BOC Sciences delivers precise mass balance and excretion data to accelerate your lead optimization and candidate selection.
Utilizing specialized metabolic cages allows for the separate, contamination-free collection of urine and feces over defined time intervals. This method is the gold standard for non-invasive excretion monitoring in rodent models during screening phases.
For compounds with low oral bioavailability or high hepatic clearance, BDC is performed to collect bile directly. This technique enables the differentiation between biliary excretion and poor absorption, crucial for structural optimization.
For non-radiolabeled compounds, we utilize high-sensitivity Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). This approach allows for the specific quantification of the parent drug and known metabolites in complex matrices like feces and bile.
Using 14C or 3H labeled compounds, Liquid Scintillation Counting (LSC) provides the most accurate mass balance data. It ensures that all drug-related material, including unknown metabolites, is accounted for in the excretion profile.
We combine high-resolution mass spectrometry (HRMS) with excretion studies to identify metabolite structures in urine and feces. This helps determine if the drug is excreted unchanged or extensively metabolized prior to elimination.
For volatile compounds or drugs labeled at positions susceptible to decarboxylation, we employ traps to collect expired CO2 or volatiles. This ensures a complete mass balance picture for specific chemical classes.
BOC Sciences optimizes excretion study protocols for a wide range of drug modalities. From traditional small molecules to complex new modalities, we customize extraction and detection strategies to ensure accurate tracking of elimination pathways.
Provide your compound details and study objectives. Our scientists will design a tailored excretion protocol to answer your specific ADME questions.
We define the study parameters (species, n-number, sampling timepoints, administration route) based on your lead optimization goals and compound properties.
Animals are acclimatized to metabolic cages to minimize stress. Compounds are administered via specified routes (PO, IV, SC, IP) with precise dosing.
Excreta are collected at scheduled intervals. Samples undergo homogenization, extraction, and rigorous analysis using LC-MS/MS or LSC methods.
A detailed research report is delivered, including mass balance calculations, cumulative excretion plots, and interpretation of elimination pathways.
Our rapid screening excretion studies help medicinal chemists understand if a structural change shifts the elimination route from renal to hepatic, allowing for the design of compounds with desirable pharmacokinetic properties.
By comparing intravenous and oral excretion data (and utilizing bile duct cannulation), we help isolate whether low bioavailability is due to poor absorption, first-pass metabolism, or rapid biliary excretion.
Excretion studies often yield higher concentrations of metabolites than plasma. We use these samples to identify and structurally characterize downstream metabolites, supporting comprehensive metabolic mapping.
We conduct parallel excretion studies in different species (e.g., Rodents vs. Non-Rodents) to evaluate interspecies differences in elimination pathways, aiding in the selection of the most relevant species for safety pharmacology.
Partner with BOC Sciences to gain a clear understanding of your compound's elimination profile. Our expert bioanalytical team delivers high-quality mass balance and excretion data to support your internal decision-making.
Our optimized sample processing and extraction protocols ensure maximum recovery of the analyte from complex matrices like feces and tissues, providing accurate mass balance data.
Equipped with state-of-the-art LC-MS/MS and radio-detection technologies, we achieve superior sensitivity and selectivity, allowing for the detection of low-level metabolites.
We customize every aspect of the study, from dosing regimens to sampling intervals, to fit the specific physicochemical properties and R&D stage of your molecule.
Our scientists don't just deliver numbers; we integrate excretion data with metabolic stability and distribution results to provide a holistic view of your compound's behavior.
Client Needs: A biotech client observed low plasma exposure for a highly lipophilic candidate and needed to determine if the drug was being rapidly excreted or accumulating in tissues.
Challenges: Standard urine analysis showed negligible drug levels. The compound's high lipophilicity made extraction from fecal homogenates difficult, resulting in poor initial recovery rates (< 60%).
Solution: BOC Sciences developed a customized fecal homogenization protocol utilizing a gradient of organic solvents and high-energy mechanical disruption (bead beating) to ensure complete solubilization of the lipophilic matrix. We subsequently executed a rigorous 120-hour mass balance study, employing validated extraction methods to maximize recovery.
Outcome: We achieved >95% mass balance recovery, revealing that 90% of the drug was excreted unchanged in feces. This confirmed poor absorption rather than rapid renal clearance, guiding the client to focus on formulation strategies to enhance solubility.
Client Needs: To select a lead candidate with minimal renal clearance (for use in patients with kidney impairment), a client needed to confirm the hepatic/biliary route as the primary elimination pathway.
Challenges: Differentiating between unabsorbed drug in feces and drug excreted via bile was impossible with standard metabolic cage studies.
Solution: We implemented a sophisticated Bile Duct Cannulation (BDC) model in rats, performed by expert surgeons to maintain physiological stability. Bile, urine, and feces were collected in separate, temperature-controlled fractions following IV administration, allowing for precise differentiation of elimination pathways.
Outcome: The study demonstrated that 70% of the dose was recovered in the bile within 24 hours, confirming biliary excretion as the dominant route. The client successfully nominated the candidate for further development targeting the specific patient population.
Client Needs: During early screening, a client detected a rapidly disappearing parent compound in plasma but found no parent drug in urine. They required identification of the major excreted forms.
Challenges: The metabolites were unknown and highly polar, making them difficult to detect with standard reversed-phase LC-MS methods used for the parent.
Solution: We conducted a comprehensive excretion study coupled with Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry (UHPLC-HRMS). Advanced metabolite identification software was utilized to screen for expected and unexpected biotransformations, correlating retention times and mass shifts to identify polar conjugates.
Outcome: We identified a glucuronide conjugate as the major component in urine. This insight clarified the clearance mechanism (Phase II metabolism) and allowed the client to assess the risk of futile cycling or toxicity associated with the metabolite.
Excretion studies aim to evaluate the rate and route by which a compound or its metabolites are eliminated through urine, feces, or other body fluids. They provide insights into in vivo clearance patterns, primary excretion organs, and potential metabolic pathways, supporting dose design and drug optimization.
Excretion analysis typically relies on LC-MS/MS, radiolabel tracing, and NMR techniques. These methods sensitively detect drugs and metabolites in body fluids, ensuring accurate characterization of excretion kinetics and supporting quantitative evaluation of in vivo behavior.
Sample collection should cover key time windows after administration to capture major excretion phases. This usually includes sequential urine and feces collection, sometimes complemented with blood or bile samples, to comprehensively describe excretion rates, proportions, and metabolite distribution for quantitative analysis and clearance evaluation.
Excretion data reveal drug clearance pathways, excretion proportions, and major metabolite types, reflecting metabolic speed and extent. These insights support structural optimization, dose adjustment, and provide experimental basis for developing new metabolic models.
Radiolabeled or stable isotope-labeled compounds allow precise tracking of drugs and metabolites in complex biological systems. Labeling enhances detection sensitivity, helps identify low-abundance metabolites, and enables quantitative assessment of overall clearance and metabolic proportions, providing reliable data for pharmacokinetic analysis.
The mass balance data provided by BOC Sciences was instrumental in our decision to redesign our lead scaffold. Their ability to accurately quantify metabolites in fecal samples saved us from advancing a compound with poor absorption properties.
— Dr. Arthur, Medicinal Chemistry Lead, Biotech Startup
The bile duct cannulation surgery and subsequent analysis were performed flawlessly. The data quality was high, and the report provided a clear picture of the elimination kinetics necessary for our internal modeling.
— Dr. Lucas, DMPK Director, Pharmaceutical Company
We needed quick excretion profiling to rank order three potential candidates. BOC Sciences delivered the results ahead of schedule, allowing us to meet our milestone deadlines for candidate selection.
— Dr. James, Senior Scientist, Drug Discovery Firm
When we faced recovery issues with our sticky compound, the team at BOC Sciences proactively developed a custom extraction method. Their dedication to getting the science right is why we continue to work with them.
— Dr. Thomas, VP of Preclinical Research
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