Metabolic Stability Calculator
Calculate Metabolic Stability
About the Metabolic Stability Calculator
The Metabolic Stability Calculator is a scientifically accurate, research-grade tool designed for pharmaceutical scientists, medicinal chemists, and drug discovery professionals. This calculator determines in vitro metabolic stability using the gold-standard half-life (t₁/₂) and intrinsic clearance (CLint) methods established in peer-reviewed literature and widely adopted by leading CROs and pharmaceutical companies worldwide.
Based on the exponential decay model of drug metabolism in liver microsomes or hepatocytes, this tool follows the exact equations published in prestigious journals such as Drug Metabolism and Disposition and recommended by the FDA and EMA for early ADME screening. Learn more about the science behind Metabolic Stability assays.
Importance of Metabolic Stability in Drug Discovery
Metabolic stability is one of the most critical parameters in early drug discovery. Poor metabolic stability leads to rapid clearance, short half-life, low bioavailability, and ultimately clinical failure. Over 40% of drug candidates fail due to suboptimal pharmacokinetic (PK) properties, with liver metabolism being the primary elimination pathway for most small-molecule drugs.
The Metabolic Stability Calculator enables researchers to quickly classify compounds as low, moderate, or high clearance risks using standardized thresholds. This early insight allows medicinal chemists to prioritize stable scaffolds, optimize metabolic soft spots, and design better drug candidates — saving millions in late-stage development costs.
Scientific Foundation and Formulas Used
This calculator uses the following peer-reviewed, industry-standard equations:
- First-order rate constant (k): k = −ln(Remaining % / 100) / Time (min)
- Half-life (t₁/₂): t₁/₂ = 0.693 / k
- Intrinsic clearance (CLint): CLint = (0.693 / t₁/₂) × (1 / Protein Concentration) × 1000 (µL/min/mg)
- Scaled Hepatic Clearance (CLH): Using well-stirred model and species-specific scaling factors
Interpretation of Results
- t₁/₂ > 60 min: High stability (desirable)
- t₁/₂ 30–60 min: Moderate stability
- t₁/₂ < 30 min: Low stability (high risk)
- CLint < 20 µL/min/mg: Low clearance
- CLint 20–50 µL/min/mg: Moderate clearance
- CLint > 50 µL/min/mg: High clearance
When and Why You Should Use This Calculator
Use the Metabolic Stability Calculator during:
- Hit-to-lead optimization
- Lead optimization phases
- Structure-metabolism relationship (SMR) studies
- Comparison of analogs in medicinal chemistry programs
- Preclinical candidate selection
- Academic research and teaching in pharmacokinetics
User Guidelines
Enter the percentage of parent compound remaining after 60 minutes of incubation with liver microsomes (standard time point). Use 0.5 mg/mL protein concentration for human/rat/mouse/dog, or 1 mg/mL for monkey if following standard protocols. Results are most accurate when NADPH is used as cofactor and Phase I metabolism is being assessed.
Benefits of Using This Tool
Instant results, no software installation required. Fully transparent calculations based on published methods. Mobile-friendly and shareable. Helps reduce animal testing by enabling better in silico/in vitro decision-making. Trusted by medicinal chemists globally.
For professional metabolic stability testing services and advanced ADME assays, visit Agri Care Hub.
References & Scientific Validation
This calculator is validated against methods published by Obach et al. (1997, 2005), FDA Guidance on Drug Interaction Studies (2020), and standard protocols from leading CROs including WuXi AppTec, Charles River, and Eurofins.
